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 lecti n 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 phosphara se SHP-1. Stimulatory receptors also bind HLA class I, lack cytoplasmi c tyrosine-based motifs, and trigger NK cell-mediated cytotoxicity. Al l these receptors are characterized by a limited diversity allowing fo r sensitive detection of loss of MHC class I molecules on autologous t ransformed and virally infected cells.