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

• Autores: Bresciani, Anne Gøther; Paul, Sinu; Schommer, Nina; Dillon, Myles B.; Bancroft, Tara; Greenbaum, Jason; Sette, Alessandro; Nielsen, Morten; Peters, Bjoern
• Año de publicación: 2016
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: BIOINFORMATICS; EPITOPES; T-CELL RECOGNITION
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

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.
Fil: Bresciani, Anne Gøther. Technical University of Denmark; Dinamarca. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Paul, Sinu. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Schommer, Nina. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Dillon, Myles B.. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Bancroft, Tara. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Greenbaum, Jason. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina. Technical University of Denmark; Dinamarca
Fil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unidos