Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom; Translational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Nuffield Department of Medicine, University of Oxford, NDM Research Building, Old Road Campus, Headington, Oxford, United Kingdom
Fiona M Powrie
Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom; Translational Gastroenterology Unit, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, United Kingdom
Michael Birnbaum
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States; Koch Institute at MIT, Cambridge, United States
Andrew J McMichael
Nuffield Department of Medicine, University of Oxford, NDM Research Building, Old Road Campus, Headington, Oxford, United Kingdom
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, United States; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, United States
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.
