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

Immunology
Anne BrescianiBjoern Peters

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.

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Citations

Aug 4, 2016·The Journal of Allergy and Clinical Immunology·Luise WesternbergBjoern Peters
Jul 9, 2016·Expert Review of Vaccines·Anne S De GrootWilliam Martin
Sep 30, 2016·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Carla OseroffAlessandro Sette
Sep 29, 2018·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Bartlomiej Swiatczak, Alfred I Tauber
Feb 12, 2020·Annual Review of Immunology·Bjoern PetersAlessandro Sette
Aug 2, 2017·American Journal of Respiratory and Critical Care Medicine·Thomas J ScribaCecilia S Lindestam Arlehamn
Mar 11, 2017·Cancer Immunology, Immunotherapy : CII·Lars Rønn OlsenGuang Lan Zhang
Dec 22, 2017·NPJ Vaccines·Kamal El BissatiRima McLeod
Jul 13, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael RasmussenSøren Buus
Nov 1, 2018·Oncoimmunology·Zeynep Koşaloğlu-YalçınBjoern Peters
Sep 12, 2021·Proceedings of the National Academy of Sciences of the United States of America·Balázs KonczMáté Manczinger

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