COMPARATIVE BINDING ANALYSIS OF CLASSICAL AND NON-CLASSICAL MHC SUPERTYPES WITH THEIR RESPECTIVE NK INHIBITORY RECEPTORS

Abstract

Natural killer (NK) cells are large granular lymphocytes that are involved in the demoliation of the cells infected by virus and the tumour cells. Natural killer (NK) cells can be defined as set of innate immune cells , carrying out continuous surveillance to detect the presence of virally infected or tumor transformed cells. In context to inhibitory signals, the human NK cells express different kinds of inhibitory receptors that are class I human leukocyte antigen (HLA) specific. These NK inhibitory receptors that are MHC specific exhibit abasic and conserved function in regulating cytolysismediated by NK cell.NK cells procure both the receptors, activating and inhibitory that comprise the total NK activity , and the summation of these opposing signals determines whether the target cell will be spared by the NK cell or not. Inhibitory signals very often override the activating signals and hence downregulate the cytotoxicity of NK cells on being recognizedby specific classI MHC molecules present on target cells. NK inhibitory receptors and non classical MHC interactions has been shown to have better inhibition of NK cell cytoxicity than the classical MHC molecule .The multifarious recognition pattern of classical and non classical MHC proteins by NK inhibitory receptors and every accessible surface involved in this binding event should be explored . The knowledge of affinity of NK cell receptor with MHC I ligands will help in understanding the binding patterns required for the inhibition of NK cell activity. The interactions between these classical and non classical MHC with their inhibitors are potentially addressable by computational approaches and can further help to develop NK based cancer therapeutic strategies.