Conservation and Variation in Human and Common Chimpanzee CD94 and NKG2 Genes

Abstract

To assess polymorphism and variation in human and chimpanzee NK complex genes, we determined the coding-region sequences for CD94 and NKG2A, C, D, E, and F from several human (Homo sapiens) donors and common chimpanzees (Pan troglodytes). CD94 is highly conserved, while the NKG2 genes exhibit some polymorphism. For all the genes, alternative mRNA splicing variants were frequent among the clones obtained by RT-PCR. Alternative splicing acts similarly in human and chimpanzee to produce the CD94B variant from the CD94 gene and the NKG2B variant from the NKG2A gene. Whereas single chimpanzee orthologs for CD94, NKG2A, NKG2E, and NKG2F were identified, two chimpanzee paralogs of the human NKG2C gene were defined. The chimpanzee Pt-NKG2CI gene encodes a protein similar to human NKG2C, whereas in the chimpanzee Pt-NKG2CII gene the translation frame changes near the beginning of the carbohydrate recognition domain, causing premature termination. Analysis of a panel of chimpanzee NK cell clones showed that Pt-NKG2CI and Pt-NKG2CII are independently and clonally expressed. Pt-NKG2CI and Pt-NKG2CII are equally diverged from human NKG2C, indicating that they arose by gene duplication subsequent to the divergence of chimpanzee and human ancestors. Genomic DNA from 80 individuals representing six primate species were typed for the presence of CD94 and NKG2. Each species gave distinctive typing patterns, with NKG2A and CD94 being most conserved. Seven different NK complex genotypes within the panel of 48 common chimpanzees were due to differences in Pt-NKG2C and Pt-NKG2D genes.

Killer Ig-like receptor (KIR) genotype and HLA ligand combinations in ulcerative colitis susceptibility

“…23 An example of NKG2D PCR-SSP typing is shown in Figure 2c. The results of the NKG2D reactions were confirmed by the direct sequencing of genomic DNA from two representative samples for each possible genotype detected (i.e.…”

“…Investigations into the possible influence of MIC polymorphism in celiac disease, a gluten-sensitive enteropathy, suggest a causal role, [16][17][18] although similar studies of IBD have produced conflicting results. [19][20][21][22] In contrast to the MIC genes, NKG2D displays limited polymorphism 23 and has not previously been investigated in susceptibility to UC.…”

Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94

“…The KIR family is important in humans and other primates, having undergone extensive diversification under positive selection. In contrast, the CD94-NKG2A system has remained relatively well conserved across the species with orthologous genes in primates and a closely related functional homolog in rodents (3,4). Consistent with the coevolution of these families and their MHC class I ligands, KIR bind polymorphic MHC class I, HLA-A, -B, and -C molecules, whereas CD94-NKG2A binds the conserved oligomorphic HLA-E molecule or the rodent homolog Qa-1 (5,6).…”

Pas de deux: Natural Killer Receptors and MHC Class I Ligands in Primates

“…The CD94 and NKG2D genes are monomorphic in the primate species tested, except for the orangutan where polymorphisms have been reported for the CD94 gene [60]. For the activating receptor genes NKG2C allelic polymorphism have been identified in primates [61][62][63]. Although the general genomic organisation of the CD94 to LY49L interval appears to be conserved in primates, particularly the activating receptor genes appear to be subject of duplications (Fig.…”

“…2). For example the chimpanzee NKG2C gene is duplicated [62] and in rhesus macaques, NKG2C is at least duplicated (own unpublished data) and several sequences have been identified that appear to be derived from duplications of the NKG2F locus [61,64]. In the orangutan, a gene has been identified that is equally related to human NKG2C and NKG2E and is thus designated NKG2CE [60].…”