Immunogenetic diversity of two South Asian cohorts: From Pakistan and India

Having critical roles in immune defense and reproduction, killer cell immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) class I ligands are encoded by the most polymorphic regions in the human genome. South Asia comprises over one quarter of the global population and harbors rich genomic diversity. Limiting our understanding of population-specific variation and disease susceptibility, high-resolution immunogenetic studies of South Asian ancestry individuals are lacking. Here, we characterize KIR and HLA class I diversity in two South Asian cohorts: sampling an urban population from Karachi, Pakistan (n = 79), and a Dravidian-speaking Yadav population from southern India (n = 70). Targeted sequencing identified 151 distinct KIR alleles across 13 genes, including 11 previously uncharacterized allotypes. Over 75% of the genotypes were KIR-Bx. We identified 98 HLA class I alleles and extensive haplotypic diversity, with all major KIR binding motifs represented, and a mean of seven potential inhibitory KIR-HLA interactions per individual (6.6 in Karachi, 7.4 in Yadav). Together, these results demonstrate substantial immunogenetic diversity and population-specific KIR and HLA variation within the two studied cohorts. This study expands knowledge of KIR and HLA diversity and offers a framework for further evolutionary and disease-focused in South Asia.