Authors: Kensuke Shibata, Chihiro Motozono, Masamichi Nagae, Takashi Shimizu, Eri Ishikawa, Daisuke Motooka, Daisuke Okuzaki, Yoshihiro Izumi, Masatomo Takahashi, Nao Fujimori, James B. Wing, Takahide Hayano, Yoshiyuki Asai, Takeshi Bamba, Yoshihiro Ogawa, Makoto Furutani-Seiki, Mutsunori Shirai, Sho Yamasaki
Published: 2022-11-14
DOI: 10.1038/s41467-022-34802-8
Source: Full article
AbstractMHC class I-related protein 1 (MR1) is a metabolite-presenting molecule that restricts MR1-reactive T cells including mucosal-associated invariant T (MAIT) cells. In contrast to MAIT cells, the function of other MR1-restricted T cell subsets is largely unknown. Here, we report that mice in which a T cell-specific transcription factor, B-cell lymphoma/leukemia 11B (Bcl11b), was ablated in immature thymocytes (Bcl11b∆iThy mice) develop chronic inflammation. Bcl11b∆iThy mice lack conventional T cells and MAIT cells, whereas CD4+IL-18R+ αβ T cells expressing skewed Traj33 (Jα33)+ T cell receptors (TCR) accumulate in the periphery, which are necessary and sufficient for the pathogenesis. The disorders observed in Bcl11b∆iThy mice are ameliorated by MR1-deficiency, transfer of conventional T cells, or germ-free conditions. We further show the crystal structure of the TCR expressed by Traj33+ T cells expanded in Bcl11b∆iThy mice. Overall, we establish that MR1-reactive T cells have pathogenic potential.