Natural killer (NK) cells are the integral component of innate immunity, and kill infected cells, tumors and stressed cells without prior sensitization. Further, they secrete inflammatory cytokines, which drive the antigen specific adaptive immunity, NK cells distinguish these abnormal cells from healthy cells through variable inhibitory and activating Killer Cell Ig-Like Receptors (KIRs). The inhibitory KIRs recognize determinants expressed on the surface of abnormal cells and subvert these unhealthy cells. Genes encoding KIRs and HLA ligands belong to polymorphic gene families located on different chromosomes, feature variation in the number and type of genes. Since the integration of signals transduced from inhibitory and activating receptors help to balance the NK cell response between tolerance of healthy cells and killing of unhealthy cells, the combinations of KIR and HLA class I molecules play an important role in human immunity and disease. The KIR genotyping test identifies the presence and absence of 15 distinct KIR genes.
The human MHC class I chain-related gene A (MICA) is located within the HLA class I region of chromosome 6. The expression, structure and function of MICA differs considerably from classical HLA class I genes. MICA proteins are considered to be markers of 'stress' in epithelial and endothelial cells, and act as ligands for cells expressing a common activating natural killer cell receptor (NKG2D). MICA molecules are highly polymorphic and the functional relevance and implications of their polymorphism in transplant rejection, autoimmune disease and cancer are emerging. MICA antibodies have been implicated in cases of humoral solid organ rejection. MICA genotyping uses luminex technology to type MICA alleles. The test targets MICA sequence polymorphisms defined by DNA-typing methods. MICA typing can be helpful in determining whether patients are matched or mismatched for MICA with their donors.