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

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

Author information

1
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
2
Department of Systems Biology, Centre for Biological Sequence Analysis, The Technical University of Denmark, Lyngby, Denmark.
3
Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, San Martín, Buenos Aires, Argentina.

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

PMID:
26789414
PMCID:
PMC4819143
DOI:
10.1111/imm.12585
[Indexed for MEDLINE]
Free PMC Article

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