@inbook {313272,
	title = {Resurrecting KIR2DP1: A Key Intermediate in the Evolution of Human Inhibitory NK Cell Receptors That Recognize HLA-C.},
	booktitle = {J Immunol},
	volume = {198},
	number = {5},
	year = {2017},
	month = {Mar 01},
	pages = {1961-1973},
	abstract = {<p>KIR2DP1 is an inactive member of the human lineage III KIR family, which includes all HLA-C-specific receptor genes. The lethal, and only, defect in KIR2DP1 is a nucleotide deletion in codon 88. Fixed in modern humans, the deletion is also in archaic human genomes. KIR2DP1 is polymorphic, with dimorphism at specificity-determining position 44. By repairing the deletion, we resurrected 11 alleles of KIR2DP1(F) , the functional antecedent of KIR2DP1 We demonstrate how K44-KIR2DP1(F) with lysine 44 recognized C1(+)HLA-C, whereas T44-KIR2DP1(F) recognized C2(+)HLA-C. Dimorphisms at 12 other KIR2DP1(F) residues modulate receptor avidity or signaling. KIR2DP1 and KIR2DL1 are neighbors in the centromeric KIR region and are in tight linkage disequilibrium. Like KIR2DL1, KIR2DP1 contributed to CenA and CenB KIR haplotype differences. Encoded on CenA, C1-specific K44-KIR2DP1(F) were stronger receptors than the attenuated C2-specific T44-KIR2DP1(F) encoded on CenB The last common ancestor of humans and chimpanzees had diverse lineage III KIR that passed on to chimpanzees but not to humans. Early humans inherited activating KIR2DS4 and an inhibitory lineage III KIR, likely encoding a C1-specific receptor. The latter spawned the modern family of HLA-C receptors. KIR2DP1(F) has properties consistent with KIR2DP1(F) having been the founder gene. The first KIR2DP1(F) alleles encoded K44-C1 receptors; subsequently KIR2DP1(F) alleles encoding T44-C2 receptors evolved. The emergence of dedicated KIR2DL2/3 and KIR2DL1 genes encoding C1 and C2 receptors, respectively, could have led to obsolescence of KIR2DP1(F) Alternatively, pathogen subversion caused its demise. Preservation of KIR2DP1(F) functional polymorphism was a side effect of fixation of the deletion in KIR2DP1(F) by micro gene conversion.</p>
},
	isbn = {0022-1767},
	url = {https://www.ncbi.nlm.nih.gov/pubmed/28122963},
	author = {Hilton, HG and Blokhuis, JH and Guethlein, LA and Norman, PJ and Parham, P}
}
