Specificity and function of immunoglobulin superfamily NK cell inhibitory and stimulatory receptors

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Abstract
Summary: 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 ill 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.