Regulation of MAIT cells through host-derived antigens

Abstract

Mucosal-associated invariant T (MAIT) cells are a major subset of innate-like T cells that function at the interface between innate and acquired immunity. MAIT cells recognize vitamin B2-related metabolites produced by microbes, through semi-invariant T cell receptor (TCR) and contribute to protective immunity. These foreign-derived antigens are presented by a monomorphic antigen presenting molecule, MHC class I-related molecule 1 (MR1). MR1 contains a malleable ligand-binding pocket, allowing for the recognition of compounds with various structures. However, interactions between MR1 and self-derived antigens are not fully understood. Recently, bile acid metabolites were identified as host-derived ligands for MAIT cells. In this review, we will highlight recent findings regarding the recognition of self-antigens by MAIT cells.

Keywords: MAIT cell; MR1 ligand; T cell development; bile acids; self-antigen.

Figure 1

Role of symbiotic bacteria in the generation and modification of MAIT cell antigens. Bacterial riboflavin biosynthesizing enzymes, such as ribA and ribD, generate 5-A-RU, which is converted to 5-OP-RU in the presence of methylglyoxal (MGO) (left). CAS is produced by sulfation of cholic acid (CA) by sulfotransferase 2a (Sult2a) in the host. CAS is further taurine-conjugated in the host by bile acid–CoA:amino acid N-acyltransferase (BAAT) or bile acid–CoA synthetase (BACS) to generate TCA7S. Most intestinal bacteria have deconjugation enzymes, bile salt hydrolases (BSH), which metabolize TCA7S to CA7S. Symbiotic bacteria are therefore required for the maintenance of both 5-OP-RU and CA7S.

Figure 2

Circulation of CA7S in the body. CA7S is mainly biosynthesized in the liver from CA, stored in the gallbladder and excreted through the intestine (left). The source of thymic CA7S is unknown (Thymus). CA7S in the bile duct may be presented to liver MAIT cells surrounding biliary epithelial cells (BEC) expressing MR1 (Liver). Sult2a expressed by enterocytes can locally produce CA7S in some intestinal areas, which might control the homeostasis of intestinal MAIT cells. Enterocyte-derived CA7S may also be transported through the enterohepatic vein (Intestine). .