title: Comprehensive Analysis of the Naturally Processed Peptide Repertoire: Differences between HLA-A and B in the Immunopeptidome.
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.
authors.affiliation: 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.
authors.forename: Ingrid M M
authors.initials: IM
authors.lastname: Schellens
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
authors.forename: Ilka
authors.initials: I
authors.lastname: Hoof
authors.affiliation: 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.
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Meiring
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Sanne N M
authors.initials: SN
authors.lastname: Spijkers
authors.affiliation: Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Martien C M
authors.initials: MC
authors.lastname: Poelen
authors.affiliation: Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Jacqueline A M
authors.initials: JA
authors.lastname: van Gaans-van den Brink
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: van der Poel
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Costa
authors.affiliation: Centre for Immunology of Infectious Diseases and Vaccines, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Cecile A C M
authors.initials: CA
authors.lastname: van Els
authors.affiliation: 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.
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.affiliation: Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
authors.forename: Can
authors.initials: C
authors.lastname: Kesmir
mesh_terms: D000483:Alleles; D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015235:HLA-B Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008457:Measles / Q000276:immunology; D008459:Measles virus / Q000502:physiology; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D040901:Proteomics
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D010446:Peptide Fragments