Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved population of innate-like T cell. MAIT cells recognise small molecule antigens, predominantly derived from the microbial vitamin B2 riboflavin metabolism pathway, presented by the monomorphic MHC-related protein 1 (MR1). MAIT cells are highly abundant in human peripheral blood and are enriched at mucosal surfaces and related organs such at the liver. While their specific physiological role remains unresolved, MAIT cells are emerging as key players in antimicrobial immunity and barrier defense.
MAIT cells are defined by the expression of a semi-invariant TCR. They express a TRAV1-2-TRAJ33 encoded α-chain of fixed CDR3α length and minor amino acid variation. This α-chain pairs with β-chains that utilise an enriched set of TRBV genes – TRBV6-1, TRBV6-4 and TRBV20-1. This unique TCR has pattern-recognition-like function allowing docking onto MR1 and recognition of contained antigen.
Using TCR analysis at both a clonal and population level, we show that MAIT TCR α-chains permit more variability than previously recognised. Mutagenesis based studies revealed that CDR3β sequence can accommodate variation in the α-chain as well as modulate differential antigen recognition. Finally, the use of MR1 tetramers has allowed us to identify MR1-reactive T cells which express TCRs that deviate markedly from the canonical MAIT TCR. This work builds on our understanding of MAIT TCR agonism and expands our knowledge of the MR1-reactive T cell repertoire. We have furthermore investigated the role of MAIT cells in disease settings including multiple myeloma.