The HLA and KIR systems—Basic mechanisms and clinical applications

Abstract

Human natural killer cells (NK cells) express multiple receptors that enable these lymphocytes of innate immunity to recognize the presence of various HLA class I molecules on target cells. An important family of these receptor types is the Killer cell Immunoglobulin-like Receptors (KIRs) that encompasses vast diversity in the human populations. KIR variation results in large differences in NK cell phenotypes and function, therefore encoding personalized diversity in NK cell responses. KIR genetics have become integrated worldwide in the regimens for hematopoietic stem cell transplantation, where KIR genotypes are utilized as biomarkers to guide donor selection and transplant design. Genetic diversity of the KIR system is two-tiered: variation in gene content, and allelic polymorphisms at KIR loci. Another level of diversity in the KIR system is generated by differences in protein expression, where variegated expression of the receptors generates a wide array of NK cell subsets within the lymphocyte population of a human individual. The repertoire of NK cell subsets that differ in function is an important factor contributing to individual differences in the innate immune response, such as those against virus infection, in tumor immunosurveillance, and in hematopoietic stem cell transplantation. In this article, we will look into the mechanisms of genetic diversification in the KIR system, KIR expression and their roles in NK cell regulation, as well as the current aspects by which the KIR and HLA systems are implemented as effective biomarkers impacting clinical medicine, with a focus on hematopoietic stem cell transplantation.