Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.

Autor: Yang X; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA., Garner LI; NDM Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Centre for Immuno-oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Zvyagin IV; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russian Federation.; Genomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation., Paley MA; Rheumatology Division, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA., Komech EA; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russian Federation.; Genomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation., Jude KM; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA., Zhao X; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA., Fernandes RA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA., Hassman LM; Department of Ophthalmology, Washington University School of Medicine, St Louis, MO, USA., Paley GL; Department of Ophthalmology, Washington University School of Medicine, St Louis, MO, USA., Savvides CS; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA.; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA., Brackenridge S; NDM Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Centre for Immuno-oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Quastel MN; NDM Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Centre for Immuno-oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Chudakov DM; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Translational Medicine, Pirogov Russian National Research Medical University, Moscow, Russian Federation.; Genomics of Adaptive Immunity Department, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russian Federation., Bowness P; Nuffield Department of Orthopaedics Rheumatology and Muscuoskeletal Science (NDORMS), Botnar Research Center, University of Oxford, Oxford, UK., Yokoyama WM; Rheumatology Division, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. yokoyama@dom.wustl.edu.; Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, USA. yokoyama@dom.wustl.edu., McMichael AJ; NDM Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, UK. andrew.mcmichael@ndm.ox.ac.uk.; Centre for Immuno-oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK. andrew.mcmichael@ndm.ox.ac.uk., Gillespie GM; NDM Research Building, Nuffield Department of Medicine, University of Oxford, Oxford, UK. geraldine.gillespie@ndm.ox.ac.uk.; Centre for Immuno-oncology, Nuffield Department of Medicine, University of Oxford, Oxford, UK. geraldine.gillespie@ndm.ox.ac.uk., Garcia KC; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA, USA. kcgarcia@stanford.edu.; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA. kcgarcia@stanford.edu.; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA, USA. kcgarcia@stanford.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Dec; Vol. 612 (7941), pp. 771-777. Date of Electronic Publication: 2022 Dec 07.
DOI: 10.1038/s41586-022-05501-7
Abstrakt: Human leucocyte antigen B*27 (HLA-B*27) is strongly associated with inflammatory diseases of the spine and pelvis (for example, ankylosing spondylitis (AS)) and the eye (that is, acute anterior uveitis (AAU)) 1 . How HLA-B*27 facilitates disease remains unknown, but one possible mechanism could involve presentation of pathogenic peptides to CD8 + T cells. Here we isolated orphan T cell receptors (TCRs) expressing a disease-associated public β-chain variable region-complementary-determining region 3β (BV9-CDR3β) motif 2-4 from blood and synovial fluid T cells from individuals with AS and from the eye in individuals with AAU. These TCRs showed consistent α-chain variable region (AV21) chain pairing and were clonally expanded in the joint and eye. We used HLA-B*27:05 yeast display peptide libraries to identify shared self-peptides and microbial peptides that activated the AS- and AAU-derived TCRs. Structural analysis revealed that TCR cross-reactivity for peptide-MHC was rooted in a shared binding motif present in both self-antigens and microbial antigens that engages the BV9-CDR3β TCRs. These findings support the hypothesis that microbial antigens and self-antigens could play a pathogenic role in HLA-B*27-associated disease.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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