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A COMMON GENOTYPE CARRIES NO FUNCTIONAL KIR GENE.
Zeying Du, Ph.D., David W. Gjertson, Ph.D., Elaine F. Reed, Ph.D. and Rajalingam Raja, Ph.D.. Los Angeles CA, USA, UCLA, 90095, UCLA Immunogenetics Center.

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To understand the complex immunogenetic relationship between Killer cell immunoglobulin-like receptors (KIR) and HLA class I ligands, we have characterized KIR genes on a panel of 387 HLA-defined US population. Most inhibitory KIR genes and one activating KIR2DS4 occur in 80-100%. KIR2DL2 and 2DL5, and all other activating KIR genes occur at 30-50%. We have further analyzed the combination of different KIR genes (termed genotypes). Forty-six distinct KIR genotypes were identified in this panel. Caucasians and Asians had 25 genotypes each, Hispanics had 20 genotypes and African Americans had 16 genotypes. Only seven genotypes found common in all four populations, five of them occur most frequently (>60%) in each population. Ten of the 46 genotypes characterized in this study were novel.
Finally we have determined the functional KIR receptors in each individual using the following criteria: 1. The inhibitory KIR genes are considered functional only if they have a relevant self-HLA ligand, whereas all activating KIR are considered to be functional. 2. KIR2DS4 was considered functional activating receptor only if it is a full-length variant. The Caucasians and African Americans have higher ratio of functional inhibitory KIR over the activating KIRs. Contrarily, Hispanics and Asians have higher frequency of activating KIR over functional inhibitory KIR. Every individual has at least one functional inhibitory KIR gene to a self HLA class I. However, 18% Caucasians 8% Hispanics 22% African Americans and 10% Asians have no activating KIR gene, and their NK activation is likely depend on lectin-like receptors. Population differences in functionally distinct KIR genes need to be explained with the susceptibility or resistance to human disease.