Abstract
MR1-restricted mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites, which are generated by a broad range of bacteria, from Escherichia coli to Mycobacterium tuberculosis and BCG. MAIT cells have been described as innate sensors of infection as they accumulate early in infected tissues. MAIT cells maintain an activated phenotype throughout the course of infections, secrete inflammatory cytokines, and have the potential to directly kill infected cells, playing an important role in shaping the host response. In this review, we will discuss the current knowledge regarding the molecular mechanisms that underline MAIT cells activation in sterile and non-sterile inflammatory conditions.
Highlights
Innate-like lymphocytes, such as invariant natural killer T cells, have gained great interest since their discovery, as these cells lie at the interface between innate and adaptive immune responses. iNKT cells are memory cells bearing a semi-invariant T cell receptor (TCR) through which they recognize self- and bacterial-derived lipid antigens presented by CD1d molecules
These results provide evidence that mucosal-associated invariant T (MAIT) cells are able to sense a wide range of bacteria through detection of vitamin metabolites, including transitory intermediates, presented by MR1 molecules
While murine studies have revealed the importance of the microbiota in shaping MAIT cell differentiation, as they are absent in germ-free mice [7], this study suggests that human MAIT cells develop prenatally, before establishment of the commensal microflora, the factors driving this maturation remain to be identified [22]
Summary
Innate-like lymphocytes, such as invariant natural killer T (iNKT) cells, have gained great interest since their discovery, as these cells lie at the interface between innate and adaptive immune responses. iNKT cells are memory cells bearing a semi-invariant T cell receptor (TCR) through which they recognize self- and bacterial-derived lipid antigens presented by CD1d molecules. These molecules can be captured and stabilized through Schiff bases with Lys in the MR1 groove These compounds are the substrates for conversion to RL-6,7diMe. Mass spectrometry analysis of MR1 refolded in the presence of culture supernatants from S. typhimurium, E. coli (DH5α), or rRL-6-CH2OH revealed species with matching properties to the synthetic 5-OP-RU, raising the possibility that the compound initially identified as MR1 ligand was 5-OP-RU [10, 13]. Mass spectrometry analysis of MR1 refolded in the presence of culture supernatants from S. typhimurium, E. coli (DH5α), or rRL-6-CH2OH revealed species with matching properties to the synthetic 5-OP-RU, raising the possibility that the compound initially identified as MR1 ligand was 5-OP-RU [10, 13] These results provide evidence that MAIT cells are able to sense a wide range of bacteria through detection of vitamin metabolites, including transitory intermediates, presented by MR1 molecules
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