GLOSSARY

T

• 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:

  The role of TLR2 in Infection and Immunity. Oliveira-Nascimento L, et al. Frontiers in Immunology (2012)

• 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.