Antigen recognition properties of semi-invariant T cell receptors

Classical alpha beta T cells express diverse T cell antigen receptors (TCR) that recognize a variety of peptides presented by MHC. However, certain classes of T cells express a more restricted TCR that recognizes other types of antigens presented by non-classical MHC molecules. We sought to understand how the Natural Killer T (NKT) cell TCR is able to respond to a variety of lipid antigens with exquisite specificity. We also characterized the TCR of Mucosal-Associated Invariant T (MAIT) cells by mutagenesis. This allowed us to understand the structural requirements for recognition MR1:antigen complexes. Lastly, we undertook analyses to characterize the antigen that is recognized by the MAIT cell TCR. Taken together, these methods allowed us to understand how the semi-invariant TCRs of NKT and MAIT cells recognize their cognate antigens.