γδ T cell antigen receptor polyspecificity enables T cell responses to a broad range of immune challenges.

Autor:	Guo J; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Chowdhury RR; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Mallajosyula V; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305., Xie J; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Dubey M; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Liu Y; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305., Li J; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305., Wei YL; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Palanski BA; Department of Chemistry, Stanford University, Stanford, CA 94305., Wang C; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Qiu L; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.; National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China., Ohanyan M; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Kask O; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305., Sola E; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305., Kamalyan L; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305., Lewis DB; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305., Scriba TJ; South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town 7700, South Africa., Davis MM; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305.; HHMI, Stanford University School of Medicine, Stanford, CA 94305., Dodd D; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305., Zeng X; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.; National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.; Research Units of Infectious disease and Microecology, Chinese Academy of Medical Sciences, Beijing 100730, China., Chien YH; Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305.; Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jan 23; Vol. 121 (4), pp. e2315592121. Date of Electronic Publication: 2024 Jan 16.
DOI:	10.1073/pnas.2315592121
Abstrakt:	γδ T cells are essential for immune defense and modulating physiological processes. While they have the potential to recognize large numbers of antigens through somatic gene rearrangement, the antigens which trigger most γδ T cell response remain unidentified, and the role of antigen recognition in γδ T cell function is contentious. Here, we show that some γδ T cell receptors (TCRs) exhibit polyspecificity, recognizing multiple ligands of diverse molecular nature. These ligands include haptens, metabolites, neurotransmitters, posttranslational modifications, as well as peptides and proteins of microbial and host origin. Polyspecific γδ T cells are enriched among activated cells in naive mice and the responding population in infection. They express diverse TCR sequences, have different functional potentials, and include the innate-like γδ T cells, such as the major IL-17 responders in various pathological/physiological conditions. We demonstrate that encountering their antigenic microbiome metabolite maintains their homeostasis and functional response, indicating that their ability to recognize multiple ligands is essential for their function. Human γδ T cells with similar polyspecificity also respond to various immune challenges. This study demonstrates that polyspecificity is a prevalent feature of γδ T cell antigen recognition, which enables rapid and robust T cell responses to a wide range of challenges, highlighting a unique function of γδ T cells. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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