Abstract
Natural killer (NK) cells are innate lymphocytes that eliminate infected and transformed cells. They discriminate healthy from diseased tissue through killer cell Ig-like receptor (KIR) recognition of HLA class I ligands. Directly impacting NK cell function, KIR polymorphism associates with infection control and multiple autoimmune and pregnancy syndromes. Here we analyze KIR diversity of 241 individuals from five groups of Iranians. These five populations represent Baloch, Kurd, and Lur, together comprising 15% of the ethnically diverse Iranian population. We identified 159 KIR alleles, including 11 not previously characterized. We also identified 170 centromeric and 94 telomeric haplotypes, and 15 different KIR haplotypes carrying either a deletion or duplication encompassing one or more complete KIR genes. As expected, comparing our data with those representing major worldwide populations revealed the greatest similarity between Iranians and Europeans. Despite this similarity we observed higher frequencies of KIR3DL1*001 in Iran than any other population, and the highest frequency of HLA-B*51, a Bw4-containing allotype that acts as a strong educator of KIR3DL1*001+ NK cells. Compared to Europeans, the Iranians we studied also have a reduced frequency of 3DL1*004, which encodes an allotype that is not expressed at the NK cell surface. Concurrent with the resulting high frequency of strong viable interactions between inhibitory KIR and polymorphic HLA class I, the majority of KIR-A haplotypes characterized do not express a functional activating receptor. By contrast, the most frequent KIR-B haplotype in Iran expresses only one functional inhibitory KIR and the maximum number of activating KIR. This first complete, high-resolution, characterization of the KIR locus of Iranians will form a valuable reference for future clinical and population studies.
Highlights
Natural killer (NK) cells are essential for human immunity to infection and cancer, and for successful reproduction [1, 2]
KIRA haplotypes are associated with controlling infectious disease and cancer, but confer susceptibility to reproductive disorders, whereas killer cell immunoglobulin like receptors (KIR)-B haplotypes are associated with protection from reproductive disorders [1, 7]
Two KIR genes were present as two copies (2N) in every individual, KIR3DL3 at the centromeric end of the KIR locus and KIR3DL2 at the telomeric end (Figure 1A)
Summary
Natural killer (NK) cells are essential for human immunity to infection and cancer, and for successful reproduction [1, 2]. To discriminate diseased from healthy tissue cells, NK cells express an array of inhibiting and activating cell surface receptors [3, 4]. Prominent among these receptors are the killer cell immunoglobulin like receptors (KIR), which educate and modulate NK cell function through interaction with HLA class I [5, 6]. KIR having a long cytoplasmic tail are inhibitory, whereas those having a short cytoplasmic tail are activating. KIRA haplotypes are associated with controlling infectious disease and cancer, but confer susceptibility to reproductive disorders, whereas KIR-B haplotypes are associated with protection from reproductive disorders [1, 7]. Haploidentical transplantation therapy for leukemia has an increased success rate when the stem cell donors carry KIR-B haplotypes [18, 19]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
