Abstract
Mucosal associated invariant T (MAIT) cells are an innate-like T cell subset prevalent in humans and distributed throughout the blood and mucosal sites. Human MAIT cells are defined by the expression of the semi-invariant TCRα chain TRAV1-2/TRAJ12/20/33 and are restricted by the non-polymorphic major histocompatibility complex (MHC) class I-like molecule, MHC-related protein 1, MR1. MAIT cells are activated by small organic molecules, derived from the riboflavin biosynthesis pathway of bacteria and fungi, presented by MR1. Traditionally, MAIT cells were thought to recognize a limited number of antigens due to usage of an invariant TCRα chain and restriction by a non-polymorphic MHC molecule. However, recent studies demonstrate that the TCR repertoire of MAIT cells is more heterogeneous, suggesting there is a more diverse array of MR1 antigens that MAIT cells can recognize. In response to infected cells, MAIT cells produce the pro-inflammatory cytokines, IFN-γ and TNF, and are cytolytic. Studies performed in MR1-deficient mice suggest that MAIT cells can provide anti-bacterial control within the first few days post-infection, as well as contribute to enhanced adaptive immunity in murine models of respiratory infections. In humans, the role of MAIT cells is unclear; however, evidence points to interplay between MAIT cells and microbial infections, including Mycobacterium tuberculosis. Given that MAIT cells are pro-inflammatory, serve in early control of bacterial infections, and appear enriched at tissue sites where microbes interface and gain access to the body, we postulate that they play an important role in antimicrobial immune responses. In this review, we discuss the most recent studies on the function and phenotype of MAIT cells, including their TCR diversity and antigenic repertoire, with a focus on the contribution of human MAIT cells in the immune response to microbial infection.
Highlights
The immune system is conceptually divided into two general categories: innate and adaptive
The antigen recognition receptor on T cells, the T cell receptor (TCR), recognizes foreign antigens only when they are bound to major histocompatibility complex (MHC) molecules, which are expressed on the cell surface of host cells
These data suggest that the increase in Mucosal associated invariant T (MAIT) cell frequencies in response to pulmonary live vaccine strain of Francisella tularensis (LVS) infections and early control of the bacteria within the lungs is MR1-dependent, but that IL-12 plays a direct role in the containment of intracellular infection
Summary
The immune system is conceptually divided into two general categories: innate and adaptive. The laboratories of McCluskey and Rossjohn successfully identified small molecules derived from the folic acid (vitamin B9) and riboflavin (vitamin B2) metabolic pathways as the first known ligands for MR1(6) They determined that metabolites from the riboflavin pathway, but not the folic acid pathway, activated Jurkat T cells expressing the invariant TCRα chain TRAV1-2 paired with TRBV6.1, TRBV6.4, or TRBV20. As described for the intracellular containment of BCG, co-incubation of purified MAIT cells with LVS-infected macrophages resulted in bacterial growth inhibition in an IL-12-dependent manner Together, these data suggest that the increase in MAIT cell frequencies in response to pulmonary LVS infections and early control of the bacteria within the lungs is MR1-dependent, but that IL-12 plays a direct role in the containment of intracellular infection
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