DOMAIN ORGANIZATION AND SEQUENCE RELATIONSHIP OF KILLER-CELL INHIBITORY RECEPTORS

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 rece ptors were identified that are likely to share specificity in HLA bind ing, 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 diffe rences in the cytoplasmic region of the proteins. The Ig-like domains, which form the extracellular segment responsible for specificity of H LA recognition, were individually shown to be characteristic of specif ic groups of receptors, and do not appear to have been assorted betwee n 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 protei ns are shown to be between 35-45% identical to those of CD89, a recept or for IgA on myeloid cells. This level of homology, combined with the ir shared localization on chromosome 19q13.4, suggests a common evolut ionary origin.