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...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
eLife Sciences Publications, Ltd
2020
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| _version_ | 1826265774958837760 |
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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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| first_indexed | 2024-03-06T20:28:55Z |
| format | Journal article |
| id | oxford-uuid:3063a2aa-5c53-42b2-a5b9-608b35386b75 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:28:55Z |
| publishDate | 2020 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| 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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