Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes.
The segregation of killer cell immunoglobulin-like receptor ( KIR) genes was determined for a panel of 21 Caucasoid families: 23 different KIR gene patterns were found and could be assigned to combinations of 16 different haplotypes. Four loci were held in common by all haplotypes: KIR2DL4, KIR3DL2, the putative pseudogene KIR3DL3 and KIR2DL2/KIR2DL3, the latter likely being alleles of one gene. Group A haplotypes, which have a unique combination of seven KIR genes, were found at 80% frequency in the family panel, the polygenic group B haplotypes at 65% frequency. KIR gene segregation was fully determined for the nine group B haplotypes, which occurred at highest frequencies in both the family panel and a panel of unrelated individuals. The group B haplotypes carried between seven and 11 KIR genes and encoded inhibitory KIR for one, two, or all three major HLA class I epitopes. Analysis of human leucocyte antigen (HLA) class I genotypes revealed that most, but not all, individuals possess an inhibitory KIR for a self HLA class I epitope. The number of stimulatory KIR genes in group B haplotypes varied considerably between one and five. The data show that group B haplotypes possess a broad spectrum of KIR gene patterns, which is largely complementary to the KIR gene set of group A haplotypes. The results suggest that rapid diversification of group B haplotypes is the result of pathogen-mediated selection for KIR genotypes that have more than the set of KIR genes provided by the group A haplotype.
Uhrberg
Markus
M
Institute for Transplantation Diagnostics and Cell Therapeutics, University Clinic of Düsseldorf, Building 14.80, Moorenstrasse 5, 40225 Düsseldorf, Germany. uhrberg@itz.uni-duesseldorf.de
Parham
Peter
P
Wernet
Peter
P
D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008297:Male; D010375:Pedigree; D016133:Polymerase Chain Reaction / Q000379:methods; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D054345:Receptors, KIR2DL4; D054347:Receptors, KIR3DL2; D044465:White People / Q000235:genetics*
D015395:Histocompatibility Antigens Class I; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; C515079:KIR2DL4 protein, human; C515084:KIR3DL2 protein, human; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D054345:Receptors, KIR2DL4; D054347:Receptors, KIR3DL2