MHC class I‐related molecule, MR1, and mucosal‐associated invariant T cells

Abstract

The MHC-related 1, MR1, molecule presents a new class of microbial antigens (derivatives of the riboflavin [Vitamin B2] biosynthesis pathway) to mucosal-associated invariant T (MAIT) cells. This raises many questions regarding antigens loading and intracellular trafficking of the MR1/ligand complexes. The MR1/MAIT field is also important because MAIT cells are very abundant in humans and their frequency is modified in many infectious and non-infectious diseases. Both MR1 and the invariant TCRα chain expressed by MAIT cells are strikingly conserved among species, indicating important functions. Riboflavin is synthesized by plants and most bacteria and yeasts but not animals, and its precursor derivatives activating MAIT cells are short-lived unless bound to MR1. The recognition of MR1 loaded with these compounds is therefore an exquisite manner to detect invasive bacteria. Herein, we provide an historical perspective of the field before describing the main characteristics of MR1, its ligands, and the few available data regarding its cellular biology. We then summarize the current knowledge of MAIT cell differentiation and discuss the definition of MAIT cells in comparison to related subsets. Finally, we describe the phenotype and effector activities of MAIT cells.

Intra-Hepatic Depletion of Mucosal-Associated Invariant T Cells in Hepatitis C Virus-Induced Liver Inflammation

“…MAIT cells play a role in the host defense against bacterial infections 7, 8 . Their semi-invariant Vα7.2-Jα33 T cell receptor recognizes vitamin B metabolites from bacteria such as E. coli presented on major histocompatibility complex class I-related molecules (MR1) 9–12 . A recent study demonstrated that MAIT cells localize around bile ducts in the portal tracts of the liver and respond to bacterial antigens 13 .…”

The role of the gastrointestinal tract in the pathogenesis of rheumatic diseases

“…It is interesting to note that anti-TNF therapy, a well established anti-inflammatory therapy in AS, results in systemic and intestinal reduction of ILC3 and in strong reduction of intestinal expression of MAdCAM1 [37]. Mucosal-associated invariant T (MAIT) cellsda novel innate-like T-cell population, recognizing a highly conserved antigen derived from the microbial riboflavin synthesis pathway [40]dhave been recently implicated in the pathogenesis of AS. Gracey E et al [41] recently demonstrated that MAIT cells are reduced in frequency in the blood of patients with AS compared with HCs.…”

MAIT cells: a novel therapeutic target for alcoholic liver disease?

“…MAIT cells are a recently identified subset of innate-like T cells with a conserved invariant T cell antigen receptor (TCR) α-chain, composed of Vα7.2-Jα33 in humans and Vα19-Jα33 in mice, and express high levels of the C-type lectin receptor CD161 or the interleukin (IL)-18 receptor α subunit 6. MAIT cells are initially called ‘mucosal-associated’ because of relative abundance of the Vα7.2-Jα33 transcript detected in human gut biopsies and the enrichment of homologous Vα19-Jα33 transcript among murine lamina propria lymphocytes compared with intraepithelial lymphocytes or mesenteric lymph nodes 7.…”

“…One major function of MAIT cells is to inhibit bacterial infection through the invariant TCR that recognises microbial riboflavin/vitamin B2 metabolites presented by the major histocompatibility complex class I-related protein 1 6. MAIT cells can be also activated by inflammatory cytokines such as IL-12 and IL-18 in a TCR-independent manner, and subsequently produce a variety of cytokines such as tumour necrosis factor-alpha, interferon gamma, IL-17 and IL-22, suggesting that in addition to their antibacterial functions, MAIT cells may play a role in modulating immune responses in various types of liver diseases 6.…”

“…MAIT cells can be also activated by inflammatory cytokines such as IL-12 and IL-18 in a TCR-independent manner, and subsequently produce a variety of cytokines such as tumour necrosis factor-alpha, interferon gamma, IL-17 and IL-22, suggesting that in addition to their antibacterial functions, MAIT cells may play a role in modulating immune responses in various types of liver diseases 6. For example, Bolte et al 12 recently reported that intrahepatic MAIT cells were depleted in patients with viral hepatitis, which was likely due to activation-induced cell death caused by inflammatory cytokines.…”