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Host Genetics and Immune Regulation
The natural killer (NK) cells and cytotoxic T lymphocytes (CTL) are the integral components of cell-mediated cytotoxicity (CMI) that govern early response to infection. The action of both NK cells and CTL is controlled by the interaction of their specific receptors with class I human leukocyte antigens (HLA) expressed on the surface of target cells. The class I receptor-repertoire of CTL comprises of T cell receptors (TCR) and accessory molecules, and the TCR diversity is generated through somatic gene rearrangements. Contrarily, the NK cell receptor-repertoire is constituted by structurally and functionally divergent products of two polygenic families: killer cell Ig-like receptors (KIR) of Ig-super gene family, and dimmers of CD94 and NKG2 proteins with lectin-like domains. Unlike TCR-repertoire, the diversity of NK cell receptor-repertoire is determined by a combined genetic, transcriptional and translational factors. Haplotypic variation in the number and type of KIR genes and allelic polymorphism of each KIR genes individualize the human genome. Further, alternative mRNA splicing and clonal expression pattern of each KIR gene diversify the NK cells within an individual. The NK cell receptors have distinct HLA specificity. Since both KIR and HLA systems are polymorphic and located on different chromosomes they segregate independently into germs cells. This produces a population diversity in the number and type of KIR:HLA pairs inherited, which determine the strength of CMI against the invading pathogens. My current research is mainly focused to understand the diversity and polymorphism of NK cell receptor repertoire, HLA class I ligands and their combinations in human health and disease
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