Diverse MR1-restricted T cells in mice and humans

Nat Commun. 2019 May 21;10(1):2243. doi: 10.1038/s41467-019-10198-w.

Abstract

Mucosal-associated invariant T (MAIT) cells express an invariant TRAV1/TRAJ33 TCR-α chain and are restricted to the MHC-I-like molecule, MR1. Whether MAIT cell development depends on this invariant TCR-α chain is unclear. Here we generate Traj33-deficient mice and show that they are highly depleted of MAIT cells; however, a residual population remains and can respond to exogenous antigen in vitro or pulmonary Legionella challenge in vivo. These residual cells include some that express Trav1+ TCRs with conservative Traj-gene substitutions, and others that express Trav1- TCRs with a broad range of Traj genes. We further report that human TRAV1-2- MR1-restricted T cells contain both MAIT-like and non-MAIT-like cells, as judged by their TCR repertoire, antigen reactivity and phenotypic features. These include a MAIT-like population that expresses a public, canonical TRAV36+ TRBV28+ TCR. Our findings highlight the TCR diversity and the resulting potential impact on antigen recognition by MR1-restricted T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Disease Models, Animal
  • HEK293 Cells
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Legionella / immunology
  • Legionellosis / immunology*
  • Legionellosis / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Minor Histocompatibility Antigens / immunology
  • Minor Histocompatibility Antigens / metabolism*
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*

Substances

  • Histocompatibility Antigens Class I
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • Mr1 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta