The development/expansion of mucosal associated invariant T cells or MAIT cells is dependent upon the class Ib molecule MR1, B cells and commensal flora. Additionally, MAIT cells express a canonical TCRα, a memory phenotype and rapidly secrete cytokines upon TCR ligation. Although these combined properties suggest that MAIT cells function as innate T cells in regulating mucosal immunity, this model has been difficult to test due to i) the paucity of MAIT cells that display MR1 specific activation in vitro, and ii) not knowing whether MR1 presents antigen. Here we show both mouse clones and human polyclonal MAIT cells display a high level of cross-reactivity on mammalian MR1 orthologs, but with differences consistent with limited ligand discrimination. Furthermore, acid eluates from recombinant or cellular MR1 proteins enhance MAIT cell activation in an MR1 specific and cross-species manner. Our combined findings demonstrate that the presentation pathway of MR1 to MAIT cells is highly physiologically conserved. These properties are reminiscent of pattern-like stimuli presented to previously described innate T cell populations and likely underlies the activated or memory phenotypes of MAIT cells.

This study was supported by grant AI046553 (Ted H. Hansen) from NIH, and in part by ANR MIME 2006 (Olivier Lantz) from the Inserm and ligue contre le cancer.