Resurrecting KIR2DP1: A Key Intermediate in the Evolution of Human Inhibitory NK Cell Receptors That Recognize HLA-C.

ABSTRACT: 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 centromer

SUBMITTER: Hilton HG 

PROVIDER: S-EPMC5321844 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature