T-cell recognition is shaped by epitope sequence conservation in the host proteome and microbiome

Anne Gøther Bresciani, Sinu Paul, Nina Schommer, Myles B. Dillon, Tara Bancroft, Jason Greenbaum, Alessandro Sette, Morten Nielsen, Bjoern Peters

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    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.
    Original languageEnglish
    JournalImmunology
    Volume148
    Issue number1
    Pages (from-to)34-39
    Number of pages6
    ISSN0019-2805
    DOIs
    Publication statusPublished - 2016

    Keywords

    • Bioinformatics
    • T-cell recognition
    • Epitopes

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