Major histocompatibility complex (MHC) class I recognition by natural killer cells

NK cells express clonally distributed receptors specific for MHC class I molecules. Structurally, these receptors belong to the C-type lectin superfamily in mouse and to the immunoglobulin superfamily in human. Functionally, they can be distinguished as inhibitory or stimulatory. Inhibitory receptors block NK cell-mediated cytotoxicity upon binding to HLA class I ligands. This function is mediated by phosphorylation of cytoplasmic tyrosines, which recruit the protein tyrosine phospharase SHP-1. Stimulatory receptors also bind HLA class I, lack cytoplasmic tyrosine-based motifs, and trigger NK cell-mediated cytotoxicity. All these receptors are characterized by a limited diversity allowing for sensitive detection of loss of MHC class I molecules on autologous transformed and virally infected cells.