Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity

T cell cross-reactivity ensures that diverse pathogen-derived epitopes encountered during a lifetime are recognized by the available TCR repertoire. A feature of cross-reactivity where previous exposure to one microbe can alter immunity to subsequent, non-related pathogens has been mainly explored f...

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Κύριοι συγγραφείς: Mendoza, JL, Fischer, S, Gee, MH, Lam, LH, Brackenridge, S, Powrie, FM, Birnbaum, M, McMichael, AJ, Garcia, KC, Gillespie, GM
Μορφή: Journal article
Γλώσσα:English
Έκδοση: eLife Sciences Publications, Ltd 2020
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author Mendoza, JL
Fischer, S
Gee, MH
Lam, LH
Brackenridge, S
Powrie, FM
Birnbaum, M
McMichael, AJ
Garcia, KC
Gillespie, GM
author_facet Mendoza, JL
Fischer, S
Gee, MH
Lam, LH
Brackenridge, S
Powrie, FM
Birnbaum, M
McMichael, AJ
Garcia, KC
Gillespie, GM
author_sort Mendoza, JL
collection OXFORD
description T cell cross-reactivity ensures that diverse pathogen-derived epitopes encountered during a lifetime are recognized by the available TCR repertoire. A feature of cross-reactivity where previous exposure to one microbe can alter immunity to subsequent, non-related pathogens has been mainly explored for viruses. Yet cross-reactivity to additional microbes is important to consider, especially in HIV infection where gut-intestinal barrier dysfunction could facilitate T cell exposure to commensal/pathogenic microbes. Here we evaluated the cross-reactivity of a ‘public’, HIV-specific, CD8 T cell-derived TCR (AGA1 TCR) using MHC class I yeast display technology. Via screening of MHC-restricted libraries comprising ~2×108 sequence-diverse peptides, AGA1 TCR specificity was mapped to a central peptide di-motif. Using the top TCR-enriched library peptides to probe the non-redundant protein database, bacterial peptides that elicited functional responses by AGA1-expressing T cells were identified. The possibility that in context-specific settings, MHC class I proteins presenting microbial peptides influence virus-specific T cell populations in vivo is discussed.
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spelling oxford-uuid:3063a2aa-5c53-42b2-a5b9-608b35386b752022-03-26T13:01:07ZInterrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3063a2aa-5c53-42b2-a5b9-608b35386b75EnglishSymplectic ElementseLife Sciences Publications, Ltd2020Mendoza, JLFischer, SGee, MHLam, LHBrackenridge, SPowrie, FMBirnbaum, MMcMichael, AJGarcia, KCGillespie, GMT cell cross-reactivity ensures that diverse pathogen-derived epitopes encountered during a lifetime are recognized by the available TCR repertoire. A feature of cross-reactivity where previous exposure to one microbe can alter immunity to subsequent, non-related pathogens has been mainly explored for viruses. Yet cross-reactivity to additional microbes is important to consider, especially in HIV infection where gut-intestinal barrier dysfunction could facilitate T cell exposure to commensal/pathogenic microbes. Here we evaluated the cross-reactivity of a ‘public’, HIV-specific, CD8 T cell-derived TCR (AGA1 TCR) using MHC class I yeast display technology. Via screening of MHC-restricted libraries comprising ~2×108 sequence-diverse peptides, AGA1 TCR specificity was mapped to a central peptide di-motif. Using the top TCR-enriched library peptides to probe the non-redundant protein database, bacterial peptides that elicited functional responses by AGA1-expressing T cells were identified. The possibility that in context-specific settings, MHC class I proteins presenting microbial peptides influence virus-specific T cell populations in vivo is discussed.
spellingShingle Mendoza, JL
Fischer, S
Gee, MH
Lam, LH
Brackenridge, S
Powrie, FM
Birnbaum, M
McMichael, AJ
Garcia, KC
Gillespie, GM
Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity
title Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity
title_full Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity
title_fullStr Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity
title_full_unstemmed Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity
title_short Interrogating the recognition landscape of a conserved HIV-specific TCR reveals distinct bacterial peptide cross-reactivity
title_sort interrogating the recognition landscape of a conserved hiv specific tcr reveals distinct bacterial peptide cross reactivity
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