Bresciani A, Paul S, Schommer N, Dillon MB, Bancroft T, Greenbaum J, Sette A, Nielsen M, Peters B. 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. PubMed PMID: 26789414; PubMed Central PMCID: PMC4819143.
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.
T-cell recognition; bioinformatics; epitopes