Specificity and function of immunoglobulin superfamily NK cell inhibitory and stimulatory receptors.
Human NK cells express clonally distributed receptors specific for HLA-A, -B and -C molecules. These receptors belong to the immunoglobulin superfamily and can be functionally 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 phosphatase SHP-1. Stimulatory receptors also bind HLA class I, lack cytoplasmic tyrosine-based motifs, and trigger NK cytotoxicity and proliferation. Both types of receptor are characterized by a limited diversity allowing for recognition of distinct class I supertypic epitopes. This limited diversity is counterbalanced by the expression of different combinations of inhibitory and stimulatory receptors with self and/or non-self HLA class I specificities on distinct NK cell clones. This peculiar strategy allows NK cells to detect loss of MHC class I molecules on autologous transformed and virally infected cells with maximal sensitivity.
Colonna
M
M
Basel Institute for Immunology, Switzerland. colonna@BII.CH
D000918:Antibody Specificity; D001667:Binding, Competitive / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D005810:Multigene Family / Q000276:immunology*; D011971:Receptors, Immunologic / Q000502:physiology*
D007136:Immunoglobulins; D011971:Receptors, Immunologic