Table 3.

Mucosal-associated invariant T cell activation and clinical implications

MAIT cell activation	Features	Clinical implications
MR1-dependent stimulation	Adaptive immune response[1,5]; Antigen-triggered MAIT cell activation[8,10,114]; MR1 undetectable before antigen exposure[140,144]; MR1 binds only small non-peptide molecules[147]; Riboflavin metabolites are main MR1 ligands[13]; Ribityllumazines are main riboflavin metabolites[13]; Bacterial and metabolic by-products can activate[9]; Drugs and drug metabolites can bind to MR1[153]	Antigens for presentation restricted[8,10]; Most microbes metabolize riboflavin[148]; Neo-antigens diversify MR1 repertoire[9]; Can develop effector memory cells[11]; Drugs can modulate MR1 signaling[153]; MR1 expression can be inhibited[155]
Modulation of MAIT cell response	Response biased by ligand and TCR β-chain[148]; Riboflavin metabolites differ among microbes[3]; CDR3β rearrangements alter antigen recognition[143]; IL-7 and non-microbial molecules can regulate[155]	Response differs among microbes[154]; TCR plasticity can affect response[143]; Local milieu modulates response[82,155]
Cytokine-dependent stimulation	Innate immune response[1,5]; Activates MAIT cells without TCR ligation[156]; Receptors for IL-7, IL-12, IL-18, IL-23, IFN-γ[81]; IL-18 is main MAIT cell activator[157,158]; IL-18 usually with other mediators[82,157,158]; IL-7, IL-18 produced by hepatocytes[81,158]; IL-1β, IL-18, IL-23 produced by monocytes[81,158]; IL-15 acts on MAIT cells directly and indirectly[158]; Bacteria elicit TLR8-induced cytokines[160]	Initiates rapid antimicrobial response[156]; Response affected by local mediators[81]; Effective against viral infections[32,33,159]; Anti-bacterial monocyte response[160]
Superantigen stimulation	Rapid powerful response to severe infection[138,163]; Bacterial exotoxins activate T cell populations[161]; Foregoes MR1 antigen activation[138,161]; Direct activation by binding to TCR Vβ[71,138,165]; Indirect activation by released IL-12, IL-18[71,138]; Generates robust release of cytokines[138]	MAIT cells are major responders[138]; May result in toxic shock[162]; Causes immune exhaustion[138,139,163]; May exacerbate autoimmune disease[168]; Induces pathogenic autoantibodies[166]

CDR3β: Complementarity-determining region 3-beta; IFN-γ: Interferon-gamma; IL: Interleukin; MAIT: Mucosal-associated invariant T; MR1: Major histocompatibility complex I-related molecule; TCR: T cell antigen receptor; TLR8: Toll-like receptor 8.