T cell receptor diversity, specificity and promiscuity of functionally heterogeneous human MR1-restricted T cells

Mol Immunol. 2021 Feb:130:64-68. doi: 10.1016/j.molimm.2020.12.009. Epub 2020 Dec 23.

Abstract

The monomorphic MHC-class I-like molecule, MR1, presents small metabolites to T cells. MR1 is the restriction element for microbe-reactive mucosal-associated invariant T (MAIT) cells. MAIT cells have limited TCR usage, including a semi-invariant TCR alpha chain and express high levels of CD161 and CD26. In addition to microbial lumazine metabolites, recent studies have demonstrated that MR1 is able to capture a variety of diverse chemical entities including folate-derivatives, a number of drug-like and other synthetic small molecules, and as yet undefined compounds of self-origin. This capacity of MR1 to bind distinct ligands likely accounts for the recent identification of additional, non-canonical, subsets of MR1-restricted T (MR1T) cells. These subsets can be defined based on their ability to recognize diverse microbes as well as their reactivity to non-microbial cell-endogenous ligands, including tumor-associated antigens. Herein, we will discuss our current understanding of MR1T cell diversity in terms of TCR usage, ligand recognition and functional attributes.

Keywords: Heterogeneity; MAIT; MR1; MR1-rescticted T cells; TCR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunity, Mucosal / immunology
  • Minor Histocompatibility Antigens / immunology
  • Minor Histocompatibility Antigens / metabolism*
  • Mucosal-Associated Invariant T Cells / immunology
  • Mucosal-Associated Invariant T Cells / metabolism*
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, Antigen, T-Cell, alpha-beta
  • T-Cell Antigen Receptor Specificity / physiology*
  • T-Lymphocyte Subsets / immunology*

Substances

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