Molecular evolution of elements controlling HLA‐C expression: Adaptation to a role as a killer‐cell immunoglobulin‐like receptor ligand regulating natural killer cell function

摘要

The regulatory elements controlling the transcription of the HLA‐A , HLA‐B , and HLA‐C genes have been extensively studied and compared. However, few studies have considered regulatory differences in the HLA genes from the perspective of their role as ligands for the killer‐cell immunoglobulin‐like receptor (KIR) family of HLA receptors expressed by natural killer (NK) cells. HLA‐C is the most recently evolved gene, and there is considerable evidence pointing to its emergence as a specialized KIR ligand playing a major role in the missing‐self recognition system of NK cells. Here I evaluate gene‐specific differences in regulatory elements of the HLA genes, showing alterations that are consistent with the adaptation of HLA‐C to a role in NK cell regulation.