Symbiotic bacteria-dependent expansion of MR1-reactive T cells causes autoimmunity in the absence of Bcl11b

Nat Commun. 2022 Nov 14;13(1):6948. doi: 10.1038/s41467-022-34802-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • Bacteria / metabolism
  • Histocompatibility Antigens Class I
  • Mice
  • Minor Histocompatibility Antigens / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta* / genetics
  • Receptors, Antigen, T-Cell, alpha-beta* / metabolism
  • Repressor Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins


  • Receptors, Antigen, T-Cell, alpha-beta
  • Minor Histocompatibility Antigens
  • Receptors, Antigen, T-Cell
  • Histocompatibility Antigens Class I
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Mr1 protein, mouse
  • Bcl11b protein, mouse
  • Repressor Proteins