In:
Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-11-14)
Abstract:
MHC 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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-022-34802-8
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
2553671-0