T-cell Recognition Is Shaped by Epitope Sequence Conservation in the Host Proteome and Microbiome

Immunology. 2016 May;148(1):34-9. doi: 10.1111/imm.12585. Epub 2016 Feb 8.

Abstract

Several mechanisms exist to avoid or suppress inflammatory T-cell immune responses that could prove harmful to the host due to targeting self-antigens or commensal microbes. We hypothesized that these mechanisms could become evident when comparing the immunogenicity of a peptide from a pathogen or allergen with the conservation of its sequence in the human proteome or the healthy human microbiome. Indeed, performing such comparisons on large sets of validated T-cell epitopes, we found that epitopes that are similar with self-antigens above a certain threshold showed lower immunogenicity, presumably as a result of negative selection of T cells capable of recognizing such peptides. Moreover, we also found a reduced level of immune recognition for epitopes conserved in the commensal microbiome, presumably as a result of peripheral tolerance. These findings indicate that the existence (and potentially the polarization) of T-cell responses to a given epitope is influenced and to some extent predictable based on its similarity to self-antigens and commensal antigens.

Keywords: T-cell recognition; bioinformatics; epitopes.

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Epitopes, T-Lymphocyte / immunology*
  • Gastrointestinal Microbiome*
  • Humans
  • Proteome*
  • T-Lymphocytes / immunology*

Substances

  • Epitopes, T-Lymphocyte
  • Proteome