Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles. Issue 133 (December 2022)

• Record Type: Journal Article
• Authors: Nagafuchi, Yasuo; Ota, Mineto; Hatano, Hiroaki; Inoue, Mariko; Kobayashi, Satomi; Okubo, Mai; Sugimori, Yusuke; Nakano, Masahiro; Yamada, Saeko; Yoshida, Ryochi; Tsuchida, Yumi; Iwasaki, Yukiko; Shoda, Hirofumi; Okada, Yukinori; Yamamoto, Kazuhiko; Ishigaki, Kazuyoshi; Okamura, Tomohisa; Fujio, Keishi
• Is Part Of: Journal of autoimmunity. Issue 133(2022)
• Publication Date: 2022-12
• Subjects: Rheumatoid arthritis -- Immune-mediated disease -- HLA -- T cell receptor -- Public clones -- Th17; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2022.102907
• Languages: English
• ISSNs: 0896-8411

Abstract

Abstract: Objective: Human Leukocyte Antigen (HLA) alleles regulate susceptibility to rheumatoid arthritis (RA) and immune-mediated diseases. This study aims to elucidate the impact of HLA alleles to T cell subsets. Methods: We performed genome-wide and HLA allele association analysis for T cell receptor (TCR) beta chain repertoire in 13 purified T cell subsets from the ImmuNexUT database, consisting of 407 donors with ten immune-mediated diseases and healthy controls. Results: HLA class II alleles were associated with TRBV gene usage and the public clones of CD4 T cells, while HLA class I alleles were associated with CD8 T cells. RA-risk and immune-mediated diseases-risk HLA alleles were associated with TRBV gene usage of naive and effector CD4 T cell subsets and public clones accumulating in Th17. Clonal diversity was independent of HLA alleles and was correlated with transcriptome changes that reflect TCR signaling. Conclusion: This study revealed in vivo evidence that both HLA alleles and environmental factors shape naive and effector TCR repertoires in RA and immune-mediated diseases patients. Highlights: Risk HLA alleles regulate TRBV gene usage of naive and effector CD4 T cells. T cell receptor (TCR) public clones accumulate in Th17 cells. Risk HLA alleles regulate T cell receptor public clones of effector CD4 T cells. TCR clonal diversity are correlated with TCR signaling transcriptome changes.