Unravelling the Immunogenetic Landscape: KIR-HLA Interactions in Chinese Northern Han

The Han Chinese are divided into Chinese Northern Han (CNH) and Chinese Southern Han (CSH) by the Yangtze River. CSH shows enriched KIR-HLA-A/B interactions due to historical migrations, while the research on CNH's KIR-HLA diversity and evolution remains insufficient. This study elucidated the KIR-HLA immunogenetic landscape in CNH and compared it with CSH and global populations. Peripheral blood samples from 530 healthy, unrelated CNH individuals were analysed for KIR and HLA-A, -B, -C genes, using the Lifecodes KIR-SSO typing and SeCore HLA genotyping kits. Data were compared with global populations using the Allele Frequency Net Database and the 13th International Histocompatibility Workshop and Conference. Statistical analyses included principal component analysis, genetic distance calculations, and hierarchical clustering. Based on the distribution of 16 KIR genes, CNH was clustered within the East Asian genetic sphere, closest to Inner Mongolia Han (distance = 0.587) and CSH (0.685). The global average KIR AA1 frequency was 29.06%, with CNH's frequency (52.1%) being substantially above this average. CNH exhibited a Δ genetic distance of -0.4 between KIR+HLA pairs and HLA ligands when compared with CSH, highlighting their close genetic relationship in KIR-HLA interactions. HLA class I haplotypes in CNH encoded more KIR ligands compared to other populations, with a significant difference between CNH and CSH (p_c = 0.017). This study showed CNH had a unique KIR-HLA profile in East Asia, with higher KIR AA1 frequencies and more KIR ligands encoded by HLA class I haplotypes, reflecting its genetic diversity and impact on immunity and disease.