GLOSSARY
#
Alternative splicing #
A process that can occur upon gene transcription, in which alternate sections of a primary gene transcript are joined to create proteins with variant amino acid sequences. Alternative splicing is typically a highly regulated and functional process in eukaryotic cells, allowing a single gene to encode several proteins. Altered function of the splicing process is common in cancer and associated with mutations and/or changes in components of the splicing machinery. Alternative splicing found in cancer cells can be of diagnostic and potentially therapeutic value.
AP-1 #
A member of the Activator Protein family of transcription factors composed of homodimers or heterodimers of members of the Fos, Jun, Maf, or ATF protein families. The AP-1 transcription factor family has been shown to affect a wide range of cellular processes, including cell growth, proliferation, differentiation, senescence, and apoptosis. AP-1 plays a role in the regulation of an immune response including effects on T cell activation, Th differentiation, and T cell anergy and exhaustion. Recent studies implicate AP-1 family members in modulating both co-stimulatory and inhibitory immune checkpoints in anti-cancer immune responses.
B7-2 (CD86) #
Alternative names:
- Human: B7-2/B70, LAB72, MGC34413, CD28LG2
- Murine: B7-2/B70, Ly-58
In humans and in mice, B7-2 can be found on the surface of: T cells, B cells, dendritic cells, macrophages/monocytes
Ligands: CD28, CD152
Function: Lymphocyte activation/costimulation, immunoregulation
Additional information: B7-2 is also known as CD86. CD86 is a ligand for CD28 and CD152 receptor molecules found on the surface of T cells. While CD86 has a similar structure and function as CD80, there are considerable differences in their protein identity, implying different stimulatory mechanisms. The exact structural and functional differences between the two are not well understood, though studies show that CD86 plays a more critical role in T cell activation. CD86 is a costimulatory molecule necessary for T cell activation and for the prevention of T cell anergy. After the MHC presents the specific antigen stimulus, the binding of CD86 with CD28 on the T cell is the second stimulus that allows T cell activation, increased IL-2 cytokine production, proliferation, and differentiation. The two-step threshold is critical for maintaining self-tolerance and inhibiting T cell overactivity. After the T cell is activated, CD152 binds to CD86 to inhibit the effector T cell’s activity, regulating the immune response.
Further reading:
What’s the difference between CD80 and CD86? Sansom DM, et al. Trends in Immunology (2003)
B7-H3 (CD276) #
Alternative names: 4lg-B7-H3, B7RP-2
B7-H3 can be found on the surface of:
- Human: dendritic cells, macrophages/monocytes
- Murine: dendritic cells, macrophages/monocytes, T cells, B cells, NK cells, epithelial cells
Ligands: TLT-2
Associated molecules: ICOS (CD278), CD28, CD152, CD26
Function: immune regulation, immune checkpoint
Additional information: B7-H3 is also known as CD276. It shows limited expression in healthy tissue and is overexpressed in tumor tissues. Increased surface expression of CD276 is correlated with tumor growth and immunosuppression by cancer cells. CD276 is, therefore, a target for immunotherapy research. CD276 has conflicting roles in immune regulation, acting as a costimulatory or co-inhibitory molecule for T cells, depending on the context.
Further reading:
B7-H3/CD276: An Emerging Cancer Immunotherapy. Zhou WT, Jin WL. Frontiers in Immunology (2021)
Cancer Research Data Commons (CRDC) #
An expandable data science infrastructure that provides access to many different data sets supported by the National Cancer Institute (NCI). Users can search and aggregate CRDC data across repositories, including the Genomic Data Commons, Clinical Trial Data Commons, Imaging Data Commons, and others.
Catalog Of Somatic Mutations In Cancer (COSMIC) #
A manually curated catalog of genes and associated mutations implicated in cancers. It is composed of two resources: COSMIC and the Cell Lines Project, as well as tools for analyzing the datasets.
COSMIC itself is divided into several projects:
- COSMIC-3D: 3D structures of mutated cancer proteins
- Cancer Gene Census: genes with mutations causally implicated in cancer
- Cancer Mutation Census: genetic variants that drive cancer
- Actionability: mutations that may be targets for treating cancers
The Cell Lines Project contains cancer cell lines, including their genomic and expression profiling data. COSMIC is managed by the Wellcome Sanger Institute.
CCR1 (CD191) #
Alternative names: CKR1, CKR-1, HM145, CMKBR1, MIP-1ɑR, RANTES-R
CCR1 can be found on the surface of:
- Human: T cells, stem cell/precursor, macrophages/monocytes
- Murine: T cells, B cells, dendritic cells, stem cell precursor, macrophages/monocytes
Ligands and associated molecules: MIP-1 (CCL3), RANTES (CCL5), MCP-3 (CCL7), MPIF-1 (CCL23), MIP-5 (CCL15), LD78
Function: chemotaxis, chemokine receptor, immune cell recruitment
Additional information: CCR1 is also known as CD191. CD191 is a receptor for various chemokines involved in cell communication and the recruitment of immune cells to inflammatory sites. In mice, CD191 acts as a receptor for the HIV virus.
CCR2 (CD192) #
Alternative names: MCP-1-R, CC-CKR-2, FLJ78307, MCG103828, MGC111760, MGC168006, MCPs receptor
In humans and in mice, CCR2 can be found on the surface of: T cells, B cells, macrophages/monocytes, granulocytes, endothelial cells
Ligands: MCP-1 (CCL2), MCP-3 (CCL7), and other MCPs, HIV-1
Function: chemotaxis, HIV receptor/coreceptor
Additional information: CCR2 is also known as CD192. Binding of CD192 by its target chemokines facilitates monocyte movement from the bone marrow into the bloodstream and moves monocytes to injured or inflamed tissues.
CCR3 (CD193) #
Alternative names: CKR3, CMKBR3, CC-CKR-3, MGC102841, MIP-1aRL2, Cmkbr1l2
CCR3 can be found on the surface of:
- Human: T cells, dendritic cells, granulocytes, epithelial cells
- Murine: T cells, dendritic cells, macrophages/monocytes, granulocytes
Ligands:
- Human: CCL5 (RANTES), CCL7 (MCP-3), CCL11 (eotaxin), CCL26 (eotaxin-3), CCL13 (MCP-4)
- Murine: CCL3, CCL5 (RANTES), CCL7 (MCP-3), CCL8, CCL11 (eotaxin), CCL14, CCL15, CCL24, CCL26 (eotaxin-3), HIV-1
Function: chemokine receptor, chemotaxis, cell adhesion, cell movement, immune response, cellular defense response
Additional information: CCR3 is also known as CD193. CD193 is a G protein-coupled receptor and receptor for multiple cytokines. Research suggests that CD193 plays a role during an allergic reaction, asthma, or parasitic infection by mediating the accumulation and activation of eosinophils and other inflammatory cells in the airway. In mice, CD193 acts as a receptor for HIV.
Further reading:
CCR4 (CD194) #
Alternative names: CC-CKR-4, CKR4, CMKBR4, ChemR13, HGCN
In humans, CCR4 can be found on the surface of: T cells, macrophages/monocytes, erythrocytes
Ligands: MIP-1 (CCL4), RANTES (CCL5), TARC (CCL17), MCP-1 (CCL2), MDC (CCL22)
Associated molecules: Caf1 and Caf4
Function: chemokine receptor, cell adhesion, homing receptor for memory lymphocytes
Additional information: CCR4 is also known as CD194. CD194 expression is greatest on the surface of Th2 cells, and is the primary chemokine receptor on Th2 cells. CD194 expression is upregulated following TCR and CD28 engagement on various T cell subsets. CD194 plays a crucial role in recruiting memory lymphocytes circulating in the blood to lymphoid tissues, specifically skin-homing T cells. CD194 associates with Caf1 and Caf4. Mogamulizumab is a therapeutic antibody targeting CCR4 that is approved to treat cutaneous T cell lymphoma.
Further reading:
CCR4 as a Therapeutic Target for Cancer Immunotherapy. Yoshie O, et al. Cancers (2021)
CCR5 (CD195) #
Less common alternative names: CMKBR5, IDDM22, CC-CKR-5, FLJ78003, AM4-7
In humans and in mice, CCR5 can be found on the surface of: T cell subsets, monocytes/macrophages, granulocytes, DCs (in mice)
Ligands: MIP-1a and -1b, MCP-2, RANTES
Function: leukocyte chemotaxis, HIV-1 co-receptor
Additional information: CCR5 regulates lymphocyte chemotaxis and migration through endothelium during inflammation. CCR5 is a co-receptor for HIV-1.
CCR6 (CD196) #
Alternative names: BN-1, DCR2, DRY6, CKRL3, GPR29, CKR-L3, CMKBR6, GPRCY4, STRL22, CC-CKR-6, KY411, Cmkbr6, CC-CKR-6
In humans and in mice, CCR6 can be found on the surface of: T cells, B cells, dendritic cells
Ligands: MIP-3a (CCL20), β-defensin
Function: cell migration, B cell maturation and differentiation
Additional information: CCR6 is also known as CD196. CD196 plays an important role in the development of B cells from the stem cell to the mature B cell. It also plays a role in the differentiation of B cells from antigen-activated mature B cells to effector plasma B cells and memory B cells. CD196 regulates dendritic cell and T cell migration and recruitment to sites of inflammation.
Further reading:
cDC1 #
A subset of dendritic cells (DCs) derived from haematopoietic stem cells. cDC1 (conventional DC1, also sometimes referred to as myeloid DC1) are found in the blood, lymph node, tonsil, spleen, bone marrow, skin, lung, intestine, and liver. cDC1 produce type III interferons and possess the machinery to efficiently cross-present intracellularly-derived antigenic peptides on MHC-I to activate CD8+ cells, playing a critical role in initiating and focusing an immune response. Recent evidence shows that cDC1 can also cross-prime CD4+ T cells via MHC-II and induce costimulation via CD40. In addition, cDC1 produce IL-12 to stimulate Th1 and NK cell responses. They also coordinate Th1 and cell killing responses through their expression of the XCR1 chemokine receptor, which supports interaction with XCL-producing activated T cells and NK cells.
cDC2 #
A subset of dendritic cells (DCs) derived from haematopoietic stem cells. cDC2 (conventional DC2, also sometimes referred to as myeloid DC2) are found in the blood, tissues (including skin, lung, intestine, and liver), and lymphoid organs. In lymph nodes, they comprise most of the other cells that are found in the T cell areas. In tonsils and spleen, cDC2 cells are mostly resident DCs derived directly from blood. cDC2 express high levels of MHC-II and are critical in promoting differentiation and activation of CD4+ T cells. They also express a broad array of lectins, TLRs, NOD-like receptors, and RIG-I-like receptors, suggesting an important role in the innate immune response. cDC2 also produce high levels of IL-12 and secrete IL-23, IL-1, andTNFɑ, but little type III interferon. Thus, they are potent activators of Th1, Th2, Th17, and CD8+ T cells.
Center for Cancer Genomics (CCG) #
A center, established at the National Cancer Institute (NCI), that leads work to catalog changes found in human tumors, unify data so that it can be shared, and support development of analytical tools and computation approaches aimed to improve analysis of large-scale, multidimensional data. Visit the CCG here.
Common gamma chain (CD132) #
Alternative names: cytokine receptor common γ chain, IL2RG/IL2Rγ, γc
Common γ chain can be found on the surface of:
- Human: T cells, B cells, NK cells, macrophages/monocytes, granulocytes
- Murine: T cells, B cells, dendritic cells, macrophages/monocytes
Associated molecules: Subunit of IL-2, IL-4, IL-7, IL-9, IL-15, IL-21 receptors; CD25, CD122, CD124, CD127, CD129, CD360, JAK3, JAK1, syk, ick
Function: functional cytokine receptor formation, signal transduction
Additional information: Common γ chain is also known as CD132. CD132 forms with other ligand-specific receptor molecules, such as CD25, CD122, CD124, CD127, CD129, and CD360 functional interleukin receptors, which play a critical role for intercellular communication. Upon cytokine binding, the JAK/STAT signaling pathway is triggered, eventually activating transcription factors that drive cell outcomes, such as lymphocyte differentiation, maturation, and proliferation.
Further reading:
CTLA-4 (CD152) #
Alternative names: Ly-56
In humans and mice, CTLA-4 can be found on the surface of: activated T cells, regulatory T cells, activated B cells
Function: T cell inhibition
Ligands: CD80 and CD86
Associated molecules: PI3-kinase, PTP1D
Additional information: CTLA-4 is also known as CD152. CD152 is constitutively expressed at high levels on the surface of regulatory T cells, and transiently upregulated on the surface of activated T cells. CD152 is homologous to CD28, and both bind to CD80 and CD86, though CD152 has higher affinity. Through interaction with CD80 or CD86 on the surface of antigen-presenting cells, CD152 plays a crucial role in regulating and preventing T cell activation against self-antigens, promoting immunological tolerance. Unlike CD28, CD152 transmits inhibitory signals to T cells, impeding cell cycle progression. Mutations in the CD152 gene have been linked to autoimmune diseases. CD152 is a target for the cancer immunotherapy drug ipilimumab (Yervoy). Yervoy blocks the interaction between CD152 and CD80/CD86, allowing T cell activation against cancer cells.
CXCR3 (CD183) #
Alternative names: CXCR3, gpr9, CKR-L2, Cmkar3, IP10, Mig-R, TAC
In humans and in mice, CXCR3 can be found on the surface of:
- Human: T cells, NK cells, stem cells/precursor, granulocytes
- Murine: T cells, B cells, NK cells, macrophages/monocytes
Ligands: IP10 (CXCL10), Mig (CXCL9), I-TAC (CXCL11), CXCL4
Function: cell adhesion, chemotaxis, leukocyte trafficking
Additional information: CXCR3 is also known as CD183. CD183 is preferentially expressed on Th1 cells. Upon chemokine binding, CD183 promotes T cell maturation and leukocyte trafficking to sites of inflammation (via integrin activation and cytoskeletal changes).
CXCR5 (CD185) #
Alternative names: Gpcr6, MGC117347, MDR15, BLR1
In humans and in mice, CXCR5 can be found on the surface of: T cells, B cells, NK cells, dendritic cells, macrophages/monocytes
Ligands and associated molecules: CXCL13 (BLC), CCL13
Function: cell migration, cell homing
Additional information: CXCR5 is also known as CD185. CD185 is a cytokine receptor. CD185 plays a role in lymphocyte recruitment and homing, particularly B cell migration. It is a surface marker for follicular helper T cells and is expressed in Burkitts’s lymphoma.
DC-SIGN (CD209/CD209a) #
Alternative names: CLEC4L, CDSIGN, CIRE
In humans and in mice, DC-SIGN can be found on the surface of: dendritic cells, macrophages/monocytes, endothelial cells
Ligands and associated molecules: CD102 (ICAM-2), CD50 (ICAM-3), mannose glycoproteins on pathogens including HIV gp120
Function: antigen endocytosis and degradation, dendritic cell migration, T cell activation, HIV receptor, pathogen receptor
Additional information: Dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) is also known as CD209. CD209 binds to CD50 to stimulate T cell proliferation. CD209 expression is upregulated by IL-4 during monocyte-to-dendritic cell differentiation. By interacting with CD102, CD209 facilitates dendritic cell migration into tissues. Furthermore, CD209 binds mannose glycoproteins found on the surface of bacterial and viral pathogens, initiating antigen endocytosis and degradation. By binding to CD209 on mucosal dendritic cells, HIV is transported to secondary lymphoid organs, where it can efficiently infect CD4+ T cells. CD209 similarly facilitates hepatitis C virus dissemination.
Further reading:
- DC-SIGN (CD209) Expression Is IL-4 Dependent and Is Negatively Regulated by IFN, TGF-β, and Anti-Inflammatory Agents. Miguel Relloso M, et al. Journal of Immunology (2002)
- DC-SIGN, a Dendritic Cell-specific HIV-1-Binding Protein that Enhances trans-Infection of T cells. Geijtenbeek TBH, et al. Cell (2000)
Dendritic Cell (DC) #
A family of bone-marrow-derived cells that are central to initiating, developing, and regulating innate and adaptive immune responses. Dendritic cells (DCs) are sentinel cells located throughout the body that capture antigens and carry them to lymphoid organs to initiate T and B cell responses. DCs are also critical in educating thymocytes and eliminating self-reactive thymocytes, inducing peripheral and central tolerance. DCs are a complex set of cells employing a wide range of mechanisms in their different roles. Recent improved classification methods employing surface markers, expression profiling,functional assays, and more, have clarified the ontogeny of DCs derived from haematopoietic stem cells (HSC). DCs can be divided into three major subsets:
- plasmacytoid DC (pDC)
- myeloid/conventional DC1 (cDC1), and
- myeloid/conventional DC2 (cDC2).
These subsets can themselves diverge to have different functionalities. In addition, HSC-derived monocytes can differentiate into subgroups of monocyte-derived DC (moDC) and monocyte-derived macrophages.
E-selectin (CD62E) #
Alternative names: ELAM-1, LECAM-2
In humans and in mice, E-selectin can be found on the surface of: endothelial cells
Ligands and associated molecules: CD162, Sialyl Lewis x/a carbohydrates
Function: cell adhesion
Additional information: E-selectin is also known as CD62E. CD62E expression on the surface of endothelial cells is activated by cytokines and the expression of CD62P. CD62E plays an important role in the body’s inflammatory response, recruiting leukocytes to inflamed areas. In inflamed tissue, macrophages release IL-1 and TNF-α, which cause endothelial cells to upregulate CD62E surface expression. Surface CD62E binds to CD162 on leukocytes that flow past the infected area at high velocity, capturing the leukocytes and mediating their tethering and rapid rolling on activated endothelium in the initial stages of inflammation.
ENCODE (ENCyclopedia Of DNA Elements) #
A program that aims to catalog all the functional elements in the human genome and genomes of model organisms (mouse, fly, worm, etc.) that determine cell function in normal and disease states, to develop and validate assays for that purpose, to develop computational tools to process the data, integrate, and analyze the data, and to make all of this available to the world’s research community. Techniques used to define the elements include, but are not limited to: profiling chromosomal transcripts to identify sequences encoding RNA for protein coding and non-coding functions and to define transcription start sites, identifying sites of chromatin accessibility, DNA methylation, protein–DNA binding, and protein–RNA binding. The program also includes identifying protein modifications that affect interactions with proteins, DNA, and RNA. An example of the type of data within ENCODE is GENCODE, an annotated database of transcribed elements in the human genome that includes transcripts of protein-coding, long non-coding RNA loci, and alternatively transcribed/spliced variants. ENCODE is an international consortium of research groups and is managed by the National Human Genome Research Institute.
Endocytic Recycling Compartment (ERC) #
Membrane-bound vesicles formed by invagination of the plasma membrane, a complex process involving the capture of extracellular and membrane-bound molecules. These endosomes typically fuse with early/sorting endosomes, and are sorted to lysosomes for degradation or trafficked through the recycling pathway to return components to the plasma membrane. Endocytic recycling is key for a variety of cellular processes, including plasma membrane homeostasis, cell shape, receptor reuse, cleavage of daughter cells in cell division, cell migration, and cell polarity.
Endoplasmic Reticulum (ER) #
A large intracellular structure defined by a membrane-enclosed space that is continuous with the perinuclear space, but separate from the cytosol. It functions as the processing domain for synthesis and export of proteins and membrane lipids, maintains calcium homeostasis, affects cell survival if subjected to stress, and is fundamental to immune functions in its role in assembly of MHC-I–antigen/peptide complexes.
ER-Golgi Intermediate Compartment (ERGIC) #
A cell compartment through which proteins destined for secretion or for the plasma membrane traffic from the endoplasmic reticulum (ER) to the Golgi complex. ERGIC clusters are thought to function as mobile transport complexes that deliver secretory cargo from ER exit sites to the Golgi.
ERGIC-53 #
A mannose-specific cargo receptor that transports glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi Intermediate Compartment (ERGIC).
Exitrons #
Internal regions of an exon that contain both protein-coding and potential splicing sequences. If RNA expressed from these exitrons is spliced, it could encode protein isoforms, including in-frame deletions or out-of-frame open reading frames, either of which could result in neoantigens. Exitrons expressed uniquely in tumor cells and not in normal tissue are referred to as tumor-specific exitrons (TSE).
FAS (CD95) #
Less common alternative names: TNFRSF6, APO-1
In humans and in mice, FAS can be found on the surface of: T cells, B cells, NK cells, macrophages/monocytes, granulocytes
Ligands: CD178 (CD95L; Fas ligand)
Function: Initiation of apoptosis, inflammation, metastatic dissemination, angiogenesis
Additional information: FAS is also known as CD95. CD95 belongs to the tumor necrosis factor (TNF) receptor superfamily. Upon ligand binding, CD95 activates formation of the Death-Inducing Signaling Complex (DISC), which leads to cell death. CD95 is also involved in non-apoptotic signaling and can promote carcinogenesis by promoting and maintaining inflammation and inducing cancer cell motility through PI3K signaling pathway activation. Furthermore, CD95 plays a role in angiogenesis by regulating endothelium survival, proliferation and function.
References:
Fas ligand (CD178) #
Alternative names: FASL, CD95L, TNFSF6, APT1LG1
In humans and in mice, Fas ligand can be found on the surface of: T cells, NK cells, granulocytes, endothelial cells, epithelial cells
Ligands and associated molecules: DcR3, CD95 (Fas), TNFRSF68, PTPN12, TNFRSF1A
Associated molecules: FADD
Function: apoptosis, signal transduction
Additional information: Fas ligand is also known as CD178. CD178 expression is upregulated upon T cell activation. Binding of CD178 by CD95 induces the Fas-mediated cell death pathway, which includes activation of the death-inducing signaling complex (DISC), leading to apoptosis. CD178 plays a critical role in preventing autoreactive immune responses and in homeostatically regulating T cell and NK cell activation.
FOXO4 #
A member of the Forkhead Box (FOX) family of transcription factors that is important in the regulation of genes involved in cell growth, proliferation, and differentiation. FOXO4’s function is regulated by post-translational modifications. Two important regulators, kinases PI3K and AKT, can phosphorylate FOXO4 and prevent it from translocating to the nucleus. Many cancers have been found to contain mutations that promote AKT phosphorylation, and thus inactivation of FOXO4, preventing proper cell cycle regulation.
FOXP3 #
A member of the Forkhead Box (FOX) family of transcription factors that is important in the regulation of genes involved in cell growth, proliferation, and differentiation. FOXP3 is mainly expressed by T cells, but is also expressed by epithelial cells in certain organs. It plays a critical role in the development of regulatory T cells by modulating the function of NFAT and NF-κB, key factors in TCR signaling. FOXP3 also induces expression of many other genes. In regulatory T cell model systems, FOXP3 has been shown to bind to promoters of genes involved in regulatory T cell function, and appears to inhibit transcription of these genes upon T cell receptor binding.
Fs-indel #
A term referring to frameshift mutations caused by out-of-frame insertions and/or deletions in a gene. The resultant RNA encodes a novel polypeptide. Expression of neoORF fs-indels in patients with cancer has been found to elicit antitumor immune responses and has been associated with clinical benefit from immunotherapy, suggesting diagnostic and potential therapeutic value in cancer therapy. The translation of a neoORF may depend on whether the RNA escapes from the nonsense-mediated decay pathway.
GENCODE #
An annotated database of transcribed elements in the human genome. Transcripts include protein-coding, long non-coding RNA loci, and alternatively transcribed/spliced variants. GENCODE is a subproject of ENCODE. It is the product of a consortium of research groups managed by the National Human Genome Research Institute.
Genomic Data Commons (GCD) #
A data sharing platform that standardizes genomic and clinical data from cancer research programs at the National Cancer Institute (NCI), including The Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Therapies (TARGET) data and data from individual researchers. The data is processed and harmonized so that it can be directly compared and used to generate higher level data. GCD aims to enable discoveries regarding the molecular bases of cancer that lead to better patient care.
Genotype-Tissue Expression Database (GTEx) #
An open access database and tissue bank for the study of tissue-specific gene expression and regulation. GTEx includes expression levels and genetic variation data from whole-genome, whole-exome, and RNAseq data from deceased adult donors with no evidence of disease. The goal is to use RNA expression levels as quantitative traits to identify genes whose expression is affected by genetic variation.
gp130 (CD130) #
Alternative names: IL6ST, IL6R-beta, IL6β, common β chain
In humans and in mice, gp130 can be found on the surface of: T cells, B cells, NK cells, macrophages/monocytes, stem cells/precursors, granulocytes, endothelial cells, dendritic cells (in mice)
Associated molecules: CD126, CNF, LIF, Oncostatin M, IL-11R, IL-6, IL-11
Function: cytokine receptor signal transduction
Additional information: gp130 is also known as CD130. CD130 forms the signal transduction component of cytokine receptors of the IL-6 receptor family and is often referred to as the common gp130 subunit. CD130 is critical for signal transduction after cytokine binding to receptor binding sites, and transmits signals of IL-6, IL-11, LIF, and CNF.
ICAM-2 (CD102) #
Alternative names: ICAM-2, LY-60
In humans and in mice, ICAM-2 can be found on the surface of: T cells, B cells, macrophages/monocytes, endothelial cells
Ligands and associated molecules: LFA-1, CD11b/CD18, Integrin ɑLβ2, MAC-1
Function: cell adhesion, costimulation, lymphocyte recirculation
Additional information: ICAM-2 is also known as CD102. CD102 facilitates the interaction between T cells and B cells during lymphocyte development. CD102 mediates the cell adhesive interactions necessary for an antigen-specific immune response, and other cellular interactions important for immune surveillance and response.
ICOS (CD278) #
Alternative names: MGC39850, AILIM, Ly115, H4
In humans and in mice, ICOS can be found on the surface of: T cells
Ligands and associated molecules: CD275 (B7-H2)
Function: costimulation, T cell development
Additional information: ICOS is also known as CD278. CD278 cell surface expression is upregulated upon T cell activation. Upon binding by CD275, CD278 induces T cell proliferation and the production of cytokines for Th2 differentiation.
ICOS Ligand (CD275) #
Alternative names: B7-H2, B7RP1, LICOS, B7RP-1, KIAA0653, ICOSLG
ICOS Ligand can be found on the surface of:
- Human: T cells, B cells, dendritic cells, macrophages/monocytes, granulocytes
- Murine: B cells, dendritic cells, macrophages/monocytes
Ligands and associated molecules: CD278 (ICOS)
Function: costimulation, T cell and B cell activation, T cell proliferation
Additional information: ICOS Ligand (ICOSL) is also known as CD275. CD275 is part of the B7 family. Upon ligand binding on B cells, CD275 promotes B cell differentiation, activation, and antibody secretion. Upon ligand binding on T cells, CD275 promotes T cell activation, proliferation, differentiation, and cytokine production.
IL-12Rβ1 (CD212) #
Alternative names: Interleukin-12 receptor β1 chain, CD212b1
IL-12Rβ1 can be found on the surface of:
- Human: T cells, B cells, NK cells
- Murine: T cells, B cells, dendritic cells, NK cells, macrophages/monocytes
Ligands: IL-12, IL-23
Associated molecules: IL-12Rβ2, IL-23R, Tyk2
Function: IL-12 and IL-23 receptor, signal transduction
Additional information: IL-12Rβ1 is also known as CD212. On its own, CD212 is a low-affinity receptor for IL-12. When CD212 associates with IL-12Rβ2, it becomes a high-affinity receptor for IL-12. The IL-12/IL-12R pathway is critical for IFNγ production and subsequent immune activation, including NK cell activation and Th1 cell differentiation. When IL-12 binds to the receptor, CD212 associates with Tyk2 while IL-12Rβ2 associates with JAK2 as part of the signaling pathway. CD212 is also a receptor for IL-23 which is a cytokine involved in inflammation and Th17 immunity.
IL-15R (CD215) #
Alternative names: IL15RA
In humans and in mice, IL-15R can be found on the surface of: T cells, B cells
Ligands: IL-15
Associated molecules: CD132, CD122
Function: Receptor for interleukin 15
Additional information: IL-15R is also known as CD215. CD215 interacts with CD132 and CD122 to form the receptor for IL-15. IL-15 is critical for formation and survival of CD8+ memory cells.
IL-18Rβ (CD218b) #
Alternative names: IL18RAP, IL-1R7, CDw218b
IL-18Rβ can be found on the surface of:
- Human: T cells, B cells, NK cells, dendritic cells, granulocytes
- Murine: T cells, NK cells, dendritic cells, macrophages/monocytes, endothelial cells
Ligands: IL-18
Associated molecules: CD218a
Function: Receptor for IL-18
Additional information: IL-18Rβ is also known as CD218b. CD218b associates with CD218a to form the heterodimeric receptor for IL-18. CD218b is the signal-transducing chain of the receptor complex, whereas CD128a is the ligand-binding chain. CD218a has a low affinity to IL-18, but when associated with CD218b, the binding affinity is increased. The IL-18 signal pathway is critical for the production and release of various cytokines and expression of adhesion molecules involved in the Th1 and Th2 inflammatory response.
Further reading:
IL-21R (CD360) #
IL-21R can be found on the surface of:
- Human: T cells, B cells, NK cells, dendritic cells, granulocytes, macrophages/monocytes, stem cells
- Murine: T cells, B cells
Ligands: IL-21
Associated molecules: CD132, JAK-1, JAK-3 and STAT
Function: Receptor for IL-21
Additional information: IL-21R is also known as CD360. CD360 is a type I cytokine receptor and forms a receptor complex with the common gamma chain cytokine receptor subunit (CD132). Binding of IL-21 activates the Janus-kinase pathway and downstream, the STAT signaling pathway. The IL-21/IL-21R pathway is crucial for increasing T cell differentiation and proliferation, NK cell differentiation and cytotoxicity, and differentiating B cells into antigen-specific memory B cells.
IL-2Rα (CD25) #
Alternative names: Tac antigen, p55, TCGFR, Ly-43
In humans and mice, IL-2Rα can be found on the surface of: T cells, B cells, NK cells, macrophages/monocytes
Ligands: IL-2 (interleukin-2)
Associated molecules: CD122
Function: IL-2 receptor
Additional information: IL-2Rα is also known as CD25. Along with other markers, CD25 is a surface marker used to identify regulatory T cells (Tregs). CD25 is the alpha chain of the IL-2 receptor and forms together with CD122 and CD132 to form high-affinity IL-2 receptors.
IL-2Rβ (CD122) #
Alternative names: p70-75, IL-2 and IL-15 receptor β chain
In humans and in mice, IL-2Rβ can be found on the surface of: T cells, B cells, NK cells, macrophages/monocytes
Ligands: IL-2, IL-15
Associated molecules: CD25, CD132, Syk, Lck, Jak1, Stat5
Function: β subunit of the IL-2 and IL-15 receptor, Signal transduction
Additional information: IL-2Rβ is also known as CD122. CD122 is the beta subunit of the IL-2 receptor and IL-15 receptor. Both IL-2 and IL-15 are critical cytokines in the signaling pathways that lead to naive and memory T cell development and effector functions. Recent research has focused on blocking CD122 to promote immune tolerance to transplants. The CD122/IL-15 and CD122/IL-2 pathways play a definitive role in inducing NK cell maturation and maintaining NK cell cytotoxic activity against infection. CD122 expression is upregulated on the surface of NK cell progenitors in preparation for differentiation/maturation.
IL-3RA (CD123) #
Alternative names: IL3R, IL3RAY, IL3RX, IL3RY, MGC34174, hIL-3Ra
In humans and in mice, IL-3RA can be found on the surface of: dendritic cells, endothelial cells, granulocytes, macrophages/monocytes, stem cells/precursors
Ligands: IL-3
Associated molecules: CD131
Function: Interleukin-3 receptor
Additional information: IL-3RA is also known as CD123. CD123 is the IL-3-specific alpha subunit of the IL-3 receptor and forms a complex with CD131 (the common beta chain). IL-3 signals through the heterodimeric IL-3 receptor complex and stimulates proliferation and differentiation.
IL-4 receptor ɑ chain (CD124) #
Alternative names: IL4RA, IL4R
IL-4 receptor ɑ chain can be found on the surface of:
- Human: T cells, B cells, stem cells/precursors, macrophages/monocytes, epithelial cells
- Murine: T cells, B cells, dendritic cells, granulocytes, epithelial cells
Ligands: IL-4, IL-13
Associated molecules: CD132, Jak1, Fes, Stat6, IRS-2
Function: Interleukin-4 and Interleukin-13 receptor
Additional information: IL-4 receptor ɑ chain is also known as CD124. CD124 is the alpha chain of the IL-4 and IL-13 receptors. CD124 interacts with CD132 to form a functional receptor. IL-4 or IL-13 signaling pathways are important for IgE production, differentiation of Th2 cells, alternative activation of B cells, and the regulation of CD20 levels on B cells.
IL-7Rα (CD127) #
Alternative names: p90
In humans and mice, IL-7Rα can be found on the surface of: T cells, precursor cells, macrophages/monocytes
Function: receptor for IL-7 and thymic stromal lymphopoietin (TSP), T cell maturation and proliferation.
Ligands: IL-7, TSLP
Associated molecules: CD132, Fyn, lyn, Jak1, P13-Kinase, Lck
Additional information: IL-7Rα is also known as CD127. CD127, together with CD132, forms the IL-7 receptor. Binding of IL-7 to the IL-7 receptor causes a signal cascade that stimulates the first stage of thymic T cell development by protecting from apoptosis and promoting VDJ TCR recombination. CD127 signaling is crucial for the survival of mature T cells within the periphery. CD127 transcription and expression is homeostatically controlled in a negative feedback loop by IL-7 levels. CD127, together with the TSLP receptor chain (TSLPR or CRLF2), forms a high-affinity receptor for TSLP, which plays a pivotal role in T cell maturation, promoting T cell proliferation, driving T helper cytokine production, and inducing dendritic cell polarization.
Further reading:
Immune Checkpoint Blockade (ICB) #
A type of immunotherapy aimed at blocking interactions involving important regulatory molecules on immune cells (immune checkpoints) that modulate immune responses. Interactions between these molecules can activate or suppress an immune response. Key examples of immune checkpoint molecules include CTLA-4, PD-1, PD-L1, TIM3, LAG3, OX40, GITR, and others. Blockade of interactions between these molecules and their ligands have dramatically improved anti-cancer immunotherapy by enhancing anti-cancer immune responses. Additional immune checkpoint molecules have been identified and are being studied to assess the clinical benefit of blocking their interactions.
Immune Checkpoints #
A group of molecules that regulate immune responses. Immune checkpoints can be present on T cells, antigen-presenting cells, and tumor cells in the tumor bed and periphery. Interactions between the molecules can activate or suppress an immune response. Key examples of immune checkpoint molecules include CTLA-4, PD-1, PD-L1, TIM3, LAG3, OX40, GITR, and others.
Immune Epitope Database and Analysis Resource (IEDB) #
A searchable compilation of immune response-related antigens and epitopes relevant to infectious disease, allergy, autoimmunity, and transplantation in humans and other species. IEDB also provides tools to assist in predicting and analyzing immune epitopes. IEDB is supported by the National Institute of Allergy and Infectious Diseases.
International ImMunoGeneTics information system® (IMGT) #
An access point and resource of sequence, structure, antibodies, and web resources relevant for studying B and T cell receptors, major histocompatibility (MHC) molecules, the immunoglobulin and major histocompatibility superfamily, and related proteins of the immune system of vertebrates and invertebrates. Visit IMGT here.
L-selectin (CD62L) #
Alternative names:
- Human: LECAM-1, MEL-14, Leu8, TQ1, LAM-1
- Murine: LECAM-1, Lnhr, Ly-22, Ly-m22, Lyam-1, Lyam1
In humans and in mice, L-selectin can be found on the surface of: T cells, B cells, NK cells, macrophages/monocytes, granulocytes
Ligands and associated molecules: CD162, CD34, GlyCAM-1, MAdCAM-1
Function: cell adhesion
Additional information: L-selectin is also known as CD62L. By contributing to leukocyte tethering and rolling on activated endothelium, CD62L plays an essential role in lymphocyte homing to peripheral lymph nodes and sites of inflammation. Upon antigen encounter and T cell activation in the lymph nodes, CD62L is shed from the cell surface. T cells can then exit the lymph node, enter circulation, and exert their effector functions.
In conjunction with other markers, most notably CD45RO or CD45RA, CD62L is used to distinguish T cell differentiation states. CD62L is expressed on naive T cells (Tnaive), central memory T cells (TCM) and stem memory T cells (TSCM), but not on effector memory T cells (TEM), or effector memory T cells re-expressing CD45RA (TEMRA).
LFA-3 (CD58) #
In humans, LFA-3 can be found on the surface of: T cells, B cells, dendritic cells, NK cells, macrophages/monocytes, granulocytes, erythrocytes, endothelial cells, epithelial cells
Ligands: CD2 (LFA-2)
Function: cell adhesion
Additional information: LFA-3 is also known as CD58. Binding of CD58 to CD2 facilitates the interaction between antigen-presenting cells and T cells, as well as the interaction between cytotoxic cells and target cells. Stimulation of CD58 results in increased T cell and NK cell activity.
LRP1 (CD91) #
Alternative names: APOER, APR, ɑ2M-R, ɑ2MR
In humans, LRP1 can be found on the surface of: macrophages/monocytes, epithelial cells
Ligands and associated molecules: RAP, ɑ2M, apoE, Lactoferrin, LDLs
Function: phagocytosis, intracellular signaling, lipid homoeostasis
Additional information: LRP1 is also known as CD91. CD91 is important for receptor mediated endocytosis. CD91 mediates the phagocytosis and degradation of apoptotic cells and other ligands.
M1 macrophage #
A subset of macrophages that are present in tissues and are similar to macrophages activated by LPS and IFNγ in vitro. M1 macrophages produce high levels of IL-12, low levels of IL-10, and have pro-inflammatory and phagocytic functions that can have antitumor benefits. They also have anti-microbial activities. M1 macrophages are one end of a broad continuum of macrophage subtypes with different immunologic functions. M2 macrophages are at the opposite end of the continuum.
M2 macrophage #
A subset of macrophages that are present in tissues, and are associated with wound or tissue repair. M2 macrophages produce anti-inflammatory molecules such as IL-10, TGFβ, and only low levels of IL-12. Their phenotype can be enhanced with IL-4. M2 macrophages are often found to be associated with tumors and may promote tumor growth. M2 macrophages are one end of a broad continuum of macrophage subtypes with different immunologic functions. M1 macrophages are at the opposite end of the continuum.
MHC #
A collection of genes coding for the major histocompatibility complex (MHC) molecules. MHC molecules are found on the surface of nucleated cells of the body. There are two classes of MHC molecules (MHC class-I and MHC class-II). Both are central to educating the immune system to recognize self and non-self molecules, and play a role in initiating immune responses to pathogens, variant or inappropriately expressed self molecules, or neoantigens (as in cancer cells), or self molecules in autoimmune diseases. Both types of MHC molecules are dimeric transmembrane glycoproteins.
- MHC class-I molecules are present on all nucleated cells and display peptides derived from normal intracellular self-antigens as well as from abnormal and nonself intracellular pathogens. Peptide–MHC-I molecules are recognized by CD8+ T cells.
- MHC class-II molecules are primarily found on the surface of “professional antigen-presenting cells”, e.g., macrophages, dendritic cells, and B cells, and display peptides from abnormal and nonself pathogen antigens. Peptide–MHC-II molecules are recognized by CD4+ T cells.
MHC-I #
A class of MHC molecules that are made of an α chain coupled with the smaller β2 microglobulin. MHC-I α chains are encoded by autosomal, highly polymorphic genes. Within the human population, each individual typically has three different MHC-I genes (HLA-A, HLA-B and HLA-C) and hence, 6 MHC-I alleles in total. Mice have two to three different MHC-I genes (H-2K, H-2D, and H-2L), depending on the mouse model. The MHC-I α chain forms a cleft that displays short antigen peptides (epitopes), typically 8–12 amino acids in length, to the immune system. Peptides displayed by MHC-I molecules are derived from degraded cytosolic proteins that are transported into the endoplasmic reticulum (ER) by the TAP complex, and loaded in the ER onto MHC-I molecules by the peptide loading complex. Thus, peptides displayed on MHC-I molecules include those from cellular proteins and cytosolic pathogens. Peptide–MHC-I molecules are recognized by CD8+ T cells.
MHC-II #
A class of MHC molecules that are made of an α and β chain that are similar in length. MHC-II α and β chains are encoded by autosomal, highly polymorphic genes. Within the human population, each individual typically has three sets of MHC-II genes (HLA-DR, HLA-DP and HLA-DQ, each with at least one separate gene encoding the α and β chains) and hence 12 or more MHC-II alleles in total. Mice have one to two sets of MHC-II genes (I-A and I-E), depending on the mouse model. The α and β chains of MHC-II molecules together form a cleft that displays short antigen peptides (epitopes), typically greater than 12 amino acids in length, to the immune system. Peptides displayed on MHC-II are derived from extracellular proteins captured by endocytosis, digested in lysosomes and loaded on MHC-II molecules prior to their migration to the cell surface. Thus, peptides displayed on MHC-II molecules include those from extracellular pathogens and cellular debris. Peptide–MHC-II molecules are recognized by CD4+ T cells.
Monocyte-derived Dendritic Cells #
A set of cells that have been considered to be a type of dendritic cells (DCs), though there is no clear consensus on their precise lineage. Surface markers and expression profiling support their DC characterization, but monocyte-derived dendritic cells (moDC) at sites of inflammation are heterogeneous and may also include cells with macrophage-like markers. Recent data show that moDCs or “inflammatory DCs” can develop independently of standard DC differentiation factors, FLT3 and GM-CSF. Thus, they are more likely a distinct type of cell of monocytic origin with some functionality shared with DCs. Monocytic DCs can cross-present antigen and have been used extensively as a source of ex vivo prepared antigen presenting cells for vaccines.
MS-GF+ #
A mass spectrometry (MS) database search tool that identifies peptides from a protein sequence database by comparing their MS/MS spectra versus submitted data. It can use data from a variety of MS instruments and different experimental protocols. The software can be downloaded from Pacific Northwest National Lab.
Neoantigen #
A class of novel antigens that arise in cancer, but not normal cells. They are the result of mutations, mRNA variations, and/or aberrant translation, leading to expression of novel polypeptides, or are produced by oncogenic viruses integrated into the genome. If processed and presented on MHC molecules in tumor cells or picked up and presented on antigen presenting cells, neoantigens can promote antitumor immune responses.
neoORF #
A term referring to novel (neo) open reading frames in a gene transcript. NeoORFs may be created by frameshift mutations due to out-of-frame insertions or deletions (fs-indels) or gene fusions that have occurred in the gene that result in a novel polypeptide sequence. Alternative splicing events in a primary transcript of the wild-type gene(s) can also generate neoORFs. Expression of neoORFs in patients with cancer has been found to elicit antitumor immune responses and has been associated with clinical benefit from immunotherapy, suggesting diagnostic and potential therapeutic value in cancer therapy. The translation of a neoORF may depend on whether the RNA escapes from the nonsense-mediated decay pathway.
netMHCIIpan #
A bioinformatic tool that predicts peptide binding to MHC-II molecules. It uses artificial neural networks trained on binding affinity and eluted ligand data from human MHC class-II isotypes HLA-DR, HLA-DQ, HLA-DP, and mouse H-2-IA or H2-IE. Predictions can be made for any MHC class-II of known sequence and peptides of any length, and, based on extrapolation from MHC structural information, can be used for MHC alleles for which no binding or eluted ligand data has been collected. netMHCIIpan is supported by Technical University of Denmark (DTU).
netMHCpan #
A bioinformatic tool that predicts peptide binding to MHC molecules. It uses artificial neural networks trained on binding affinity and eluted ligand data from humans, mice, cattle, primates, swine, equines, and dogs. Predictions for binding to MHC-I molecules in the netMHCpan database can be made for peptides of any length, and, based on extrapolation from MHC structural information, can be used for MHC alleles for which no binding or eluted ligand data has been collected. Predictions for binding to uploaded custom MHC-I molecules can also be made. netMHCpan is supported by the Technical University of Denmark (DTU).
NKG2D (CD314) #
Alternative names: KLRK1
In humans and in mice, NKG2D can be found on the surface of: T cells, B cells, NK cells, macrophages/monocytes, granulocytes
Ligands: MICA, MICB, ULBP2, ULBP1, H60 (mice)
Associated molecules: DAP10 dimer or DAP10 and DAP12 (in mice)
Function: MHC-1 HLA-E molecule recognition, NK cell activation
Additional information: NKG2D is also known as CD314. CD314 is a key activating receptor on NK cells. CD314 is also a costimulatory molecule on T cells and promotes the development of memory CD8+ T cells. CD314 expression on the surface of B cells plays a key role in B cell proliferation and differentiation and the regulation of IgE production. Ligands of CD314 are homologous to MHC class I molecules, and come from the MIC or RAET1/ULBP family. The expression of NKG2D ligands is induced during cellular stress (e.g., infection, senescence) or genomic stress (e.g., mutations, increased proliferation, viral replication).
NKp46 (CD335) #
Alternative names: Ly-94, NCR1
In humans and in mice, NKp46 can be found on the surface of: NK cells
Ligands: Viral glycoproteins (hemagglutinins), Heparan sulfate proteoglycans
Associated molecules: CD3ζ and FcεRIγ
Function: NK cell cytotoxicity, NK cell activation
Additional information: NKp46 is also known as CD335. CD335 is part of the natural cytotoxicity receptor (NCR) family. CD335 plays a role in antitumor and antiviral immunity, conferring tumor cell recognition and binding of viral hemagglutinins. Engagement of CD335 on NK cells results in increased cytokine production and cytotoxicity. CD335 is expressed on the surface of activated and resting NK cells.
OT-I transgenic mice and T cells #
A transgenic mouse line created to contain the OVA-specific CD8+ T cell receptor from the H2-Kb-restricted OVA257-254 (SIINFEKL)-specific CTL clone 149.42 (Kelly et al., 1993) (originally called OVA-tcr-II mice). cDNAs encoding the complete 149.42 α-chain and the genomic β-chain construct, pKS913.CB16.31 (Carbone et al., 1992) were co-injected into blastocysts from (B6 x bm1) Fl mice and progeny of the founder line, 243-2, were backcrossed to B6 mice. OT-1 mice, their naive- or antigen-stimulated T cells, and derivatives have been used extensively to study MHC-I-restricted T cell development and selection, immune tolerance, autoimmune disorders, and antitumor immune responses.
OT-II transgenic mice and T cells #
A transgenic mouse line engineered to express CD4+ T cells that express an OVA-specific αβ TCR. The TCR cDNAs were cloned from T cell hybridoma, Clone 1.1, which was derived from a C57BL/6 (B6) mouse primed with whole ovalbumin in Complete Freund’s Adjuvant. Clone 1.1 is CD4+, MHC-II I-Ab-restricted, and specific for the OVA323-339 peptide. The TCR beta chain is expressed under the control of its natural regulatory elements to successfully generate mice that express the introduced TCR in peripheral T cells and respond to the OVA antigen (Barnden et al., 1998). OT-II mice, their naive- or antigen-stimulated T cells, and derivatives have been used extensively to study MHC-II-restricted T cell development and selection, immune tolerance, autoimmune disorders, and antitumor immune responses.
OX40L (CD252) #
Alternative names: GP34, TNFSF4, TXGP1, CD134L
In humans and in mice, OX40L can be found on the surface of: B cells, dendritic cells, endothelial cells
Ligands and associated molecules: CD134 (OX40)
Function: T cell proliferation, cytokine production, costimulation
Additional information: OX40L is also known as CD252. CD252 belongs to the TNF superfamily and binds to CD134 (OX40), which is expressed on activated T cells. CD252–CD134 binding plays an important role in T cell proliferation and survival, promotes the formation of memory T cells, and induces polarization towards Th2. Surface expression of CD252 is upregulated in the presence of inflammatory signals. On the surface of activated B cells, CD252 enhances immunoglobulin secretion.
P-selectin (CD62P) #
Alternative names: GMP-140, PADGEM
In humans and in mice, P-selectin can be found on the surface of: platelets and endothelial cells
Ligands: CD162 (PSGL-1)
Associated molecules: CD24
Function: cell adhesion, platelet aggregation
Additional information: P-selectin is also known as CD62P. CD62P is constitutively expressed in platelet precursors and endothelial cells. It is stored in granules until activation of these cells leads to surface expression. CD62P expression is critical for homing leukocytes to inflamed areas. Surface CD62P binds to CD162 on leukocytes that flow past the infected area at high velocity, capturing the leukocytes and mediating their tethering and rolling on activated endothelium in the initial states of inflammation. CD62P on the surface of platelets facilitates platelet aggregation. In cancer, CD62P mediates metastasis.
PD-L2 (CD273) #
Alternative names: B7DC, MGC142238, bA574F11.2, MGC142238, MGC142240, bA574F11.2, PDCD1LG2
In humans and in mice, PD-L2 can be found on the surface of: T cells, dendritic cells, macrophages/monocytes.
Ligands: PD-1 (CD279)
Function: costimulation, inhibition, regulation of T cell proliferation
Additional information: PD-L2 is also known as CD273. CD273 interacts with CD279 to inhibit T cell proliferation and cytokine production, playing an important role in establishing immune tolerance and limiting autoimmunity. CD273 has also been shown to have immune-activating effects by inducing IL-12 production in dendritic cells.
pDC #
A subset of dendritic cells (DCs) derived from haematopoietic stem cells. Plasmacytoid DCs (pDCs) detect and respond rapidly to viral infections to produce high quantities of type I and type III interferons and cytokines, and may play a role in chronic infections. Conversely, pDC may also play a role in autoimmune diseases. The ability of pDC to sense self-nucleic acids and to produce type I interferon has been implicated in the pathogenesis of psoriasis and systemic lupus erythematosus. pDC have also been shown to induce T cell tolerance, and perhaps contribute to tumor progression.
PSGL-1 (CD162) #
Alternative names: P-Selectin-IgG fusion protein (in mice)
In humans and in mice, PSGL-1 can be found on the surface of: T cells, B cells, monocytes/macrophages, stem cells, granulocytes
Ligands: E- (CD62E), P- (CD62P) and L-(CD62L) selectins
Function: cell adhesion, host–virus interaction
Additional information: P-selectin glycoprotein ligand (PSGL-1) is also known as CD162. CD162 is expressed on all myeloid and lymphoid lineages. Its expression level differs between cell types. Myeloid cells constitutively express functioning CD162, while T cells express a modified form that must be activated during T cell activation. CD162 plays a crucial role in leukocyte capture at infected tissue by mediating the tethering and rapid rolling of leukocytes on activated endothelium in the initial stages of inflammation. As the leukocyte flows at high velocity past the tissue, CD162 binds with E-, P- and L-selectins presented on the surface of the endothelial cell, which preempts attachment, rolling, and subsequent transmigration of the leukocyte into the tissue, where it may exert its effector functions.
Further reading:Pyroptosis #
A cell death program characterized by lysis and the release of pro-inflammatory signals that elicit inflammatory responses from neighboring cells. Pyroptosis can be set off by pathological stimulation, including microbial infection, stroke, heart attack, and cancer. Intracellular danger signals trigger the formation of the inflammasome, activation of caspases, proinflammatory cytokines, and pore-forming gasdermins in the affected cells. Assembled gasdermin pores in the cell membrane then facilitate pyroptosis of the cell by water influx, cell membrane rapture, and the release of cytokines and other danger signals.
RNAseq #
A nucleotide sequencing and computational technology used to identify and quantify RNA expressed in biological samples. A variety of sequencing and computational strategies may be used, all based on the general strategy of purifying RNA from samples, generating cDNA fragments from the purified RNA, adding adaptors to one or both ends of the fragments, and obtaining short sequence reads from one or both ends of the the cDNA fragments. In some circumstances the cDNA fragments are selected by an exome capture probe-set in order to limit sequencing to exomic regions. Computational techniques are used to align the sequences to a reference genome or exome to identify the transcripts’ 5’ and 3’ ends, splicing sites, and post-transcriptional modifications, and to quantify expression levels. The methods are also used to analyze for expression of mutated alleles, and determine if structural alterations are present (small insertions or deletions [indels]) or alternative splicing. Throughput is high, resolution is to a single nucleotide, dynamic range of expression quantification is high, the required amount of RNA is low, and relative cost is low. Techniques for sequencing long fragments of RNA, either directly or as cDNA, are rapidly becoming available, allowing more direct detection of RNA structural variants such as alternative splicing or mis-splicing.
SIRPα (CD172a) #
Alternative names: SIRPA, SHPS-1, BIT, MFR, MYD-1, P84, SHPS-1, SHPS1, SIRP
In humans and in mice, SIRPα can be found on the surface of: dendritic cells, granulocytes, macrophages/monocytes, stem cells/precursors
Ligands: CD47, PTPN11
Associated molecules: SHP-2
Function: signal transduction, cell adhesion, macrophage fusion
Additional information: SIRPα is also known as CD172a. CD172a is a negative regulator of downstream kinase signaling cascades and binds to CD47 (the “don’t eat me” signal). By associating with SHP-2 after CD47 binding, CD172a negatively regulates the downstream signal pathways controlled by epidermal growth factor, thus reducing cell growth, migration, and transformation. CD172a is critical to preventing phagocytosis of self, promoting self-tolerance. CD172a is also involved in macrophage fusion, which leads to the formation of giant cells. CD47 binding prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. In various cancer types, CD172a expression is downregulated.
Further reading:
Molecular functions of SIRPα and its role in cancer. Takahashi S. Biomedical reports (2018)
Spliceosome #
A macromolecular complex of 5 small nuclear RNAs (snRNAs) and approximately 100 proteins that removes introns from precursor RNAs and joins the remaining exon sections to generate an mRNA. The spliceosome forms on a gene's primary RNA transcript, catalyzing the splicing process as the gene is transcribed. The snRNAs are critical for recognizing specific sites in the pre-mRNA and for catalyzing the process. Each of the snRNAs binds one or more of a set of specific proteins known as splicing factors, which are the protein components of the spliceosome. Transcription and splicing occur concurrently in mammalian cells, suggesting potential regulatory interactions.
TAP (Transporter Associated with antigen Processing) #
A protein complex composed of TAP-1 and TAP-2 proteins involved in transporting peptides from the cytoplasm to the endoplasmic reticulum (ER) and central to the antigen presentation machinery and, hence, initiation of immune responses. TAP is found in the lumen of the ER associated with the peptide loading complex, which consists of MHC-I, tapasin, ERp57, and calreticulin. Defects in the expression and function of antigen presentation components, including downregulation of TAP-1, have been found in solid and hematologic malignancies, and are associated with tumor immune evasion, growth, and metastasis.
The Cancer Genome Atlas (TCGA) #
A catalog of genomic, epigenomic, transcriptomic, and proteomic data obtained from cancer and matched normal tissue collected from 20,000 patients with a total of 33 different types of cancer. TCGA was created to develop a large, publicly available database that could be used to identify causes, pathways, classification groupings, druggable targets, and biomarkers, and serve as a resource for new analyses. The program ended in 2016 and its resources are now part of the broader Genomic Data Commons. Resources for using and navigating TCGA are available at resources for TCGA users.
TLR1 (CD281) #
Alternative names: rsc786, KIAA0012, MGC104956, MGC126311, MGC126312, TIL.LPRS5, DKFZp547I0610, DKFZp564I0682
TLR1 can be found on the surface of:
- Human: macrophages/monocytes, granulocytes
- Murine: dendritic cells, macrophages/monocytes
Ligands: Bacterial lipoproteins
Associated molecules: CD282 (TLR2) (in mice)
Function: activation of an innate immune response, recognition of bacterial pathogens, TLR2 regulator (in mice)
Additional information: TLR1 is also known as CD281. CD281 is part of the Toll-like receptor (TLR) family. CD281 recognizes bacterial lipoproteins. Upon PAMP recognition, CD281 mediates cytokine production and signal pathways that activate the innate immune response against pathogens. CD281 has been shown to form a heterodimer with CD282 (TLR2) and to regulate TLR2 in mice.
TLR2 (CD282) #
Alternative names: Toll-like receptor 2, TIL4, Ly105
TLR2 can be found on the surface of:
- Human: granulocytes, macrophages/monocytes
- Murine: T cells, dendritic cells, macrophages/monocytes, granulocytes
Ligands: Peptidoglycan, Lipoproteins
Associated molecules: CD286 (TLR6), CD281 (TLR1)
Function: activation of an innate immune response, recognition of bacterial pathogens
Additional information: TLR2 is also known as CD282. CD282 recognizes gram-positive bacteria, mycobacteria, and yeast, mediating an innate immune response to these pathogens via stimulation of NF-κB. In some cases, CD282 interacts with other Toll-like receptors, CD286 (TLR6) or CD281 (TLR1), to recognize pathogen-associated molecular patterns (PAMPs).
TLR3 (CD283) #
Alternative names: Toll-like receptor 3, AI957183
TLR3 can be found on the surface of:
- Human: T cells, B cells, dendritic cells
- Murine: dendritic cells, granulocytes, epithelial cells
Ligands: double-stranded RNA (dsRNA)
Function: activation of an innate immune response, recognition of viral pathogens
Additional information: TLR3 is also known as CD283. CD283 recognizes double-stranded RNA (dsRNA) from viral pathogens. Upon binding to the dsRNA, CD283 activates the NF-κB pathway and the production of Type 1 interferons, which promote inflammation and the initiation of the immune response against the viral pathogen.
TLR4 (CD284) #
Alternative names: hToll, ARMD10, Ly87, Ran/M1, Rasl2-8
In humans and in mice, TLR4 can be found on the surface of: macrophages/monocytes, granulocytes, T cell subsets
Ligands: Lipopolysaccharides (LPS)
Associated molecules: Ly96 (MD2), CD14
Function: activation of an innate immune response, recognition of bacterial pathogens
Additional information: TLR4 is also known as CD284. CD284 is a member of the Toll-like receptor (TLR) family. CD284, together with CD14 and Ly96 (MD2), recognizes lipopolysaccharides found in most gram-negative bacteria. CD284 acts via MYD88, TRRAP, and TRAF6, inducing cytokine secretion and activating the innate immune response against the bacterial pathogens.
TLR6 (CD286) #
Alternative names: Toll-like receptor 6
TLR6 can be found on the surface of:
- Human: dendritic cells, macrophages/monocytes, epithelial cells
- Murine: macrophages/monocytes, granulocytes, endothelial cells
Ligands: diacylated lipopeptides
Associated molecules: MyD88, TRAF6, CD282 (TLR2)
Function: activation of an innate immune response, recognition of bacterial pathogens
Additional information: TLR6 is also known as CD286. CD286 forms a heterodimer with CD282 (TLR2) to recognize pathogen-associated molecular patterns (PAMPs) from gram-positive bacteria, mycoplasma, fungi, some viruses, and protozoa. Upon PAMP recognition, CD286 mediates cytokine production and initiates signal pathways that act via MYD88 and TRAF6, and activates an innate inflammatory immune response against the pathogens.
Further reading:
TRAIL (CD253) #
Alternative names: APO-2L, TNFSF10, TL2, Ly81
TRAIL is found on the surface of:
- Human: T cells, B cells, macrophages/monocytes
- Murine: macrophages/monocytes
Ligands: CD261 (APO2, DR4,TRAILR1), CD262 (DR5, TRAILR2)
Function: apoptosis
Additional information: TRAIL is also known as CD253. Binding of CD253 to death receptors 4 and 5 (CD261 and CD262) induces cell death by activating the caspase-8-dependent apoptotic pathways.
Transcription Factors (TF) #
A group of proteins that interact with promoters, enhancers, and with other transcription factors at genetic loci to modulate a gene’s transcription. Transcription factors (TFs) bind to short DNA motifs with relatively low specificity. Thus, complex mechanisms are involved in providing specificity, including mechanisms such as combinatorial occupancy of DNA regulatory elements by several TFs, protein–protein interactions with other TFs, cooperativity by protein–protein interactions, or by affecting higher order chromatin structure. Putative TFs represent ~8% of human genes. Mutations in TFs are often highly deleterious and are associated with many diseases, including cancers.
TREM-1 (CD354) #
TREM-1 can be found on the surface of:
- Human: T cells, B cells, NK cells, dendritic cells, granulocytes, macrophages/monocytes
- Murine: granulocytes, macrophages/monocytes
Associated molecules: DAP12, TLRs
Function: stimulation of the inflammatory response
Additional information: TREM-1 is also known as CD354. CD354, also known as the triggering receptor expressed on myeloid cells 1 (TREM1), is a member of the immunoglobulin superfamily. CD354 further stimulates neutrophils, monocytes and macrophages in an inflammatory response by increasing the production and release of inflammatory cytokines. CD354 amplifies the inflammatory response induced by Toll-like receptor ligands. CD354 is expressed on monocytic myeloid-derived suppressor cells (mMDSC), tumor-associated macrophages (TAMs), and tumor-associated neutrophils (TANs), and is studied as a target in cancer immunotherapy.
