MR1, an immunological periscope of cellular metabolism

Abstract

The discovery that major histocompatibility complex (MHC) class I-related molecule 1 (MR1) presents microbial antigens to mucosal-associated invariant T (MAIT) cells was a significant scientific milestone in the last decade. Surveillance for foreign metabolically derived antigens added a new class of target structures for immune recognition. The recent identification of a second family of MR1-restricted T cells, called MR1T cells, which show self-reactivity suggests the microbial antigens characterized so far may only represent a handful of the potential structures presented by MR1. Furthermore, the reactivity of MR1T cells towards tumours and not healthy cells indicates tight regulation in the generation of self-antigens and in MR1 expression and antigen loading. These novel and exciting observations invite consideration of new perspectives of MR1-restricted antigen presentation and its wider role within immunity and disease.

Keywords: MAIT; MR1T cells; antigen presentation; metabolite antigens; tumour metabolites.

Graphical Abstract

Fig. 1.

Cellular alterations that may lead to MR1–ligand generation. Professional antigen-presenting cells or other healthy cells such as epithelial cells may undergo stress through different mechanisms. The cells may also be located near to inflammation or physical damage, undergo transformation or proliferate, which leads to an altered metabolism of the cell. The change in composition of metabolites that bind MR1 causes up-regulation to the cell surface, which is registered by MR1T cells to cause an effector function. Cy, cytoplasm; EE, early endosome; Ly, lysosome.