To learn how to improve vaccine design, Kessler et al. inspected the immunopeptidome from monocyte-derived DCs that were pulsed with 12 hepatitis B virus-based synthetic long peptides (SLPs) combined with either the TLR1/2 ligand Amplivant or TLR3 ligand polyI:C. The choice of adjuvant had no effect on SLP cross-presentation, but the immunopeptidome differed between DCs treated with either adjuvant, reflecting biological processes. Antigen presentation was dominated by B alleles. 14 of 33 identified SLP-derived HLA-peptides were novel potential T cell epitopes that were not predicted in silico and were often identified in more than 1 of 6 donors.
Contributed by Ute Burkhardt
ABSTRACT: Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant¨) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.
Author Info: (1) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Biomolecular Mass Spectrometry and Proteomics, Bijvoet
Author Info: (1) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical sciences, University of Utrecht, Utrecht, The Netherlands. (2) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. (3) Proteomics Center, Department of Biochemistry, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. (4) Proteomics Center, Department of Biochemistry, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. (5) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Merus N.V., Utrecht, The Netherlands. (6) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Division of Laboratories, Pharmacy and Biomedical Genetics, UMC Utrecht, Utrecht, The Netherlands. (7) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands. (8) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. (9) Proteomics Center, Department of Biochemistry, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. (10) Department of Gastroenterology & Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. s.buschow@erasmusmc.nl.
