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Updated: Aug 28, 2025

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
Control of naive and effector CD4 T cell receptor repertoires by rheumatoid-arthritis-risk HLA alleles
Yasuo Nagafuchi1, Mineto Ota1, Hiroaki Hatano2
1Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan; Department of Functional Genomics and Immunological Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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.
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