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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.

KIR Variation in Iranians Combines High Haplotype and Allotype Diversity With an Abundance of Functional Inhibitory Receptors