Human NK Cells utilize a repertoire of peptide-MHC-recognizing activating and inhibitory receptors, called KIRs, that govern their function. KIR recognition and activation are key for NK cell function, and certain KIR alleles have shown association with resistance or susceptibility to disease. While it is known that some degree of peptide specificity is inherent in KIR ligand recognition, the ‘rules’ for binding are not universally worked out. In fact, there are few if any pMHC ligands known for many KIR molecules.
We are working to systematically decode KIR recognition of peptide-MHC molecules, with the hope of understanding the molecular basis for KIR-mediated protection from or susceptibility to disease. We aim to use this data to decouple the contributions of the various (potentially opposing) interactions between different KIR alleles expressed on a given NK cell.