Regulation of NK Cell Functions Through Interaction of the CD94/NKG2 Receptors with the Nonclassical Class I Molecule HLA-E

Abstract

Natural killer (NK) cells constitute 5%–20% of the lymphocyte population in the periphery. They are cytotoxic, but also secrete cytokines. They play a major role in innate immunity, as an early defense against a variety of infections and influence the development of acquired immunity. They also participate in the elimination of certain tumors and virally infected cells which have lost or downregulated their MHC class I molecules. This concept was originally proposed by Kärre as “the missing self hypothesis” (Kärre 1997). The cytotoxic activity of NK cells is regulated by cell surface receptors for MHC class I molecules that can deliver activatory or inhibitory signals. The characterization of these receptors has considerably increased in the last few years (Lanier 1998). They are generally classified into two main families: the immunoglobulin superfamily and the C-type lectin superfamily. In humans, NK receptors belonging to the Ig superfamily can recognize groups of HLA class I molecules, such as two distinct groups of HLA-C alleles (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DS1, KIR2DS2), one group of B alleles displaying Bw4 supertypic specificity (KIR3DL1), and the HLA-A alleles, HLA-A3 and HLA-A11 (KIR3DL2). CD94/NKG2 heterodimers belong to the C-type lectin superfamily and were thought to recognize most HLA class I molecules.