ULBP4/RAET1E is highly polymorphic in the Old World monkey.

Natural-killer group 2 member D (NKG2D) is an activating receptor that plays an important role in the immune response mediated by NK cells, γδ(+) T cells, and CD8(+) T cells. In humans, MHC class I chain-related genes and UL-16 binding protein (ULBP)/retinoic acid early transcript 1 (REAT1) gene family encode ligands for NKG2D. The rhesus and crab-eating macaques, which belong to the Old World monkeys, are widely used as non-human primate models in medical researches on the immunological process. In the present study, we investigated the polymorphisms of ULBP4/RAET1E, a member of the ULBP/RAET1 family, and found 25 and 14 alleles from the rhesus and crab-eating macaques, respectively, of which diversities were far more extended than in humans. A phylogenetic study suggested that the allelic diversification of ULBP4/RAET1E predated the divergence of rhesus and crab-eating macaques.