Comprehensive Analysis of the Naturally Processed Peptide Repertoire: Differences between HLA-A and B in the Immunopeptidome

PLoS One. 2015 Sep 16;10(9):e0136417. doi: 10.1371/journal.pone.0136417. eCollection 2015.

Abstract

The cytotoxic T cell (CTL) response is determined by the peptide repertoire presented by the HLA class I molecules of an individual. We performed an in-depth analysis of the peptide repertoire presented by a broad panel of common HLA class I molecules on four B lymphoblastoid cell-lines (BLCL). Peptide elution and mass spectrometry analysis were utilised to investigate the number and abundance of self-peptides. Altogether, 7897 unique self-peptides, derived of 4344 proteins, were eluted. After viral infection, the number of unique self-peptides eluted significantly decreased compared to uninfected cells, paralleled by a decrease in the number of source proteins. In the overall dataset, the total number of unique self-peptides eluted from HLA-B molecules was larger than from HLA-A molecules, and they were derived from a larger number of source proteins. These results in B cells suggest that HLA-B molecules possibly present a more diverse repertoire compared to their HLA-A counterparts, which may contribute to their immunodominance. This study provides a unique data set giving new insights into the complex system of antigen presentation for a broad panel of HLA molecules, many of which were never studied this extensively before.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antigen Presentation
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Line
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / genetics
  • HLA-A Antigens / immunology*
  • HLA-B Antigens / chemistry
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology*
  • Humans
  • Measles / immunology
  • Measles virus / physiology
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Proteomics*

Substances

  • HLA-A Antigens
  • HLA-B Antigens
  • Peptide Fragments

Grant support

This work was supported by a HiPo (High Potential) grant from Utrecht University, and NWO grant 823.02.014. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.