Domain organization and sequence relationship of killer cell inhibitory receptors

Abstract

Natural killer (NK) cells recognize class I HLA molecules via a family of related receptors composed of two or three Ig-like domains. Using neighbor-joining analysis of available sequences, groups of these receptors were identified that are likely to share specificity in HLA binding, which in some cases had been previously determined for individual group members. Subgroups or clades were further identified which did not appear to correlate with ligand binding, but instead reflect differences in the cytoplasmic region of the proteins. The Ig-like domains, which form the extracellular segment responsible for specificity of HLA recognition, were individually shown to be characteristic of specific groups of receptors, and do not appear to have been assorted between groups. Thus it does not appear that recombination of domains played a major role in generating diversity within regions of these proteins important for HLA binding. Finally, the Ig-like domains of KIR proteins are shown to be between 35-45% identical to those of CD89, a receptor for IgA on myeloid cells. This level of homology, combined with their shared localization on chromosome 19q13.4, suggests a common evolutionary origin.