MAITs and their mates: 'Innate-like' behaviours in conventional and unconventional T cells

Summary Most CD4 and CD8 T cells are restricted by conventional MHC-molecules and mount TCR-dependent adaptive immune responses. In contrast, MAIT, iNKT and certain γδ TCR bearing cells are characterized by their abilities to recognize antigens presented by unconventional antigen-presenting molecules and to mount cytokine-mediated TCR-independent responses in an “innate-like” manner. In addition, several more diverse T cell subsets have been described that in a similar manner are restricted by unconventional antigen-presenting molecules but mainly depend on their TCRs for activation. Vice-versa, innate-like behaviour was reported in defined subpopulations of conventional T cells, particularly in barrier sites, showing that these two features are not necessarily linked. The abilities to recognize antigens presented by unconventional antigen-presenting molecules or to mount TCR-independent responses creates unique niches for these T cells and is linked to wide range of functional capabilities. This is especially exemplified by unconventional and innate-like T cells present at barrier sites where they are involved in pathogen defense, tissue homeostasis as well as in pathologic processes.