Class II MHC self-antigen presentation in human B and T lymphocytes

PLoS One. 2012;7(1):e29805. doi: 10.1371/journal.pone.0029805. Epub 2012 Jan 27.

Abstract

Human CD4(+) T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4(+) T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • Antigen Presentation / physiology*
  • Antigen-Antibody Complex / chemistry
  • Antigen-Antibody Complex / isolation & purification
  • Autoantigens / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Blood Donors
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Cell Line, Transformed
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Models, Biological
  • Peptides / chemistry
  • Peptides / isolation & purification
  • Proteome / analysis
  • Proteome / immunology
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tandem Mass Spectrometry

Substances

  • Antigen-Antibody Complex
  • Autoantigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Peptides
  • Proteome