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

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

Author information

1
Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht, Utrecht, the Netherlands; Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
2
Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
3
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; Institute for Translational Vaccinology (Intravacc), Bilthoven, The Netherlands.
4
Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
5
Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.

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.

PMID:
26375851
PMCID:
PMC4574158
DOI:
10.1371/journal.pone.0136417
[Indexed for MEDLINE]
Free PMC Article

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