title: T-cell recognition is shaped by epitope sequence conservation in the host proteome and microbiome.
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.
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.|Department of Systems Biology, Centre for Biological Sequence Analysis, The Technical University of Denmark, Lyngby, Denmark.
authors.forename: Anne
authors.identifier: http://orcid.org/0000-0002-5144-4221
authors.initials: A
authors.lastname: Bresciani
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Sinu
authors.initials: S
authors.lastname: Paul
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Schommer
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Myles B
authors.initials: MB
authors.lastname: Dillon
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Bancroft
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Greenbaum
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.affiliation: Department of Systems Biology, Centre for Biological Sequence Analysis, The Technical University of Denmark, Lyngby, Denmark.|Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina.
authors.forename: Morten
authors.initials: M
authors.lastname: Nielsen
authors.affiliation: Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D020543:Proteome; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D020543:Proteome
keywords: T-cell recognition; bioinformatics; epitopes