Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles

Yasuo Nagafuchi, Mineto Ota, Hiroaki Hatano, Mariko Inoue, Satomi Kobayashi, Mai Okubo, Yusuke Sugimori, Masahiro Nakano, Saeko Yamada, Ryochi Yoshida, Yumi Tsuchida, Yukiko Iwasaki, Hirofumi Shoda, Yukinori Okada, Kazuhiko Yamamoto, Kazuyoshi Ishigaki, Tomohisa Okamura, Keishi Fujio

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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.

Original languageEnglish
Article number102907
JournalJournal of Autoimmunity
Volume133
DOIs
Publication statusPublished - 2022 Dec
Externally publishedYes

Keywords

  • HLA
  • Immune-mediated disease
  • Public clones
  • Rheumatoid arthritis
  • T cell receptor
  • Th17

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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