KIRGenetik

KIRGenetik is the field that studies the genetic basis of killer-cell immunoglobulin-like receptors (KIRs), a family of receptors mainly expressed on natural killer cells and some T cells. The KIR gene cluster is located on chromosome 19q13.4 within the leukocyte receptor complex and is characterized by high polymorphism and frequent copy-number variation. The repertoire of KIR genes varies between individuals and populations due to duplications, deletions, and recombination, yielding diverse haplotypes.

KIR proteins comprise various inhibitory and activating receptors. They recognize ligands from MHC class I molecules, primarily HLA class I. Inhibitory KIRs transmit negative signals upon binding, dampening NK cell activity; activating KIRs provide activating signals. The balance of signals determines NK cell responses to infected or transformed cells and to allogeneic cells during transplantation.

Genomic organization: KIR genes are arranged in a clustered region with variable content. Two common haplotype lineages, A and B, differ in gene content and receptor balance; centromeric and telomeric segments contribute to diversity. Recombination and mutation generate new alleles and copy-number variation, creating extensive diversity across individuals and populations.

Clinical relevance: KIR genotype influences natural killer cell function and has been associated with outcomes in hematopoietic stem cell transplantation, solid organ transplantation, and pregnancy. KIR–HLA interactions are studied in infectious diseases and autoimmunity; associations are often context-dependent and population-specific.

Methods and resources: KIR genotyping uses PCR-based approaches, sequencing, and allele-level typing; data are curated in databases such as the IPD-KIR resource. Because of CNV and high sequence similarity, accurate typing requires specialized methods and standardized nomenclature.