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

• DOI: 10.7554/elife.58128
• Publication Date: 2020-07-27T12:00:22Z
• Authors: Juan L Mendoza; Suzanne Fischer; Marvin H Gee; Lilian H Lam; Simon Brackenridge; Fiona M Powrie; Michael Birnbaum; Andrew J McMichael; K Christopher Garcia; Geraldine M Gille...
• Keywords: 0301 basic medicine; Antigens, Bacterial; QH301-705.5; Science; Q; Histocompatibility Antigens Class I; R; Receptors, Antigen, T-Cell; HIV; CD8 T cells; HL-60 Cells; Cross Reactions; sporosarcina newyorkensis; 3. Good health; 03 medical and health sciences; Immunology and Inflammation; Medicine; Humans; MHC; Biology (General)

T cell cross-reactivity ensures that diverse pathogen-derived epitopes encountered during a lifetime are recognized by the available TCR repertoire. A feature of where previous exposure to one microbe can alter immunity subsequent, non-related pathogens has been mainly explored for viruses. Yet additional microbes is important consider, especially in HIV infection gut-intestinal barrier dysfunction could facilitate commensal/pathogenic microbes. Here we evaluated 'public', HIV-specific, CD8 cell-derived (AGA1 TCR) using MHC class I yeast display technology. Via screening MHC-restricted libraries comprising ~2×108 sequence-diverse peptides, AGA1 specificity was mapped central peptide di-motif. Using top TCR-enriched library peptides probe non-redundant protein database, bacterial elicited functional responses AGA1-expressing cells were identified. The possibility context-specific settings, proteins presenting microbial influence virus-specific populations vivo discussed.