HLA-E IS THE LIGAND FOR THE NATURAL-KILLER-CELL CD94 NKG2 RECEPTORS/

CD94/NKG2 is a recently described receptor present on natural killer ( NK) cells and certain T cells that is composed of the CD94 chain coval ently associated with a member of the NKG2 family of molecules. Both c hains are glycosylated members of the C-type lectin superfamily. The C D94/NKG2 receptors are functionally heterogenous depending on which NK G2 family member is associated with CD94. Initially, it was thought th at CD94/NKG2 receptors recognized a broad array of HLA-A, -B and -C (c lassical), as well as the nonclassical HLA-G, MHC class I molecules. I nstead, recent data have suggested that this receptor is specific for HLA-E complexed with a peptide derived from the signal sequence (resid ues 3-11) of certain classical MHC class I molecules. Position 2 (resi due 4) in the signal sequence derived peptides appears pivotal in dete rmining whether the HLA-E/peptide complex confers resistance to NK-med iated lysis. The potential roles that the CD94/NKG2-HLA-E receptor lig and interaction might play in infection and tumor development are disc ussed.