Abstract
Class I and II human leukocyte antigens (HLA-I and HLA-II) present peptide antigens for immunosurveillance by T cells. HLA molecules also form ligands for a plethora of innate, germline-encoded receptors. Many of these receptors engage HLA molecules in a peptide sequence independent manner, with binding sites outside the peptide binding groove. However, some receptors, typically expressed on natural killer (NK) cells, engage the HLA presented peptide directly. Remarkably, some of these receptors display exquisite specificity for peptide sequences, with the capacity to detect sequences conserved in pathogens. Here, we review evidence for peptide-specific NK cell receptors (PSNKRs) and discuss their potential roles in immunity.