HLA-KIR Interactions and Immunity to Viral Infections

Host genetic factors play a central role in determining the clinical phenotype ofhuman diseases. association between two polymorphic loci in human genome,human leukocyte antigen (hla) and killer cell immunoglobulin-like receptors(kirs), and genetically complex infectious disease, particularly those of viraletiology, have been historically elusive. hence, defining the influence of geneticdiversity in hla and kirs on the outcome of viral infections has beenextensively started in clinically well-defined cohort studies. hla genes encodemolecules which present antigenic peptide fragments to t lymphocytes as centralplayers in adaptive immunity against infectious diseases. kirs are expressed onnatural killer cells which perform a crucial role in innate immunity to pathogeninfection. the effector functions of nk cells such as direct killing of infectedcells, cytokine production, and cross-talk with adaptive immune system depend onactivation of nk cells, which is determined by their surface receptors. amongthese receptors, kirs, which interact with hla class i, are mainly inhibitory andexhibit substantial genetic diversity. an extensive body of association studiesindicates a role for hla–kirs interactions in infectious diseases, autoimmunedisorders, cancer, transplantation, and reproduction. various compound hla-kirgenotypes appear to affect outcome of viral infections that suggests a role for hlaclass i diversity in innate immunity as well as adaptive immune responses. theaim of this review is focusing on the impact of hla and kir alleles and differentcombinations of these alleles on clinical outcome of viral diseases to validate thisproof-of-concept with respect to the therapeutic interventions.