KIR variability. (A) The KIR gene locus on chromosome 19 consists of 15 genes and 2 pseudogenes (shown in blue). Three conserved “framework” genes are located one at either end and one in the middle of the locus (red). These are present on all haplotypes and are inhibitory. The regions between the framework genes (between the brackets) contain a variable number of activating (green) and inhibitory (pink) KIR genes. Based on gene content KIR haplotypes have been divided into 2 primary sets: A and B. (B) Most group A haplotypes have the gene organization shown here. They contain the least genes and only a single activating KIR, 2DS4. (C) Group B haplotypes display a much greater variety of subtypes than group A. Two examples of at least 20 currently reported B haplotypes are shown here. An individual's KIR genotype is the sum of 2 haplotypes, one from each parent. (D) Multiple copies of the same KIR gene have been identified in single individuals as shown here for 2DL4. (E) Further diversification of KIR haplotypes occurs as a result of allelic polymorphism within individual genes. This is a prominent feature of group A haplotypes and 3 possible separate haplotypes arising as a result of polymorphisms within the 2DL3, 2DL1, 3DL1, and 3DL2 genes are shown here. More than 20 group A haplotypes emerging as a result of allelic polymorphism have been described. (Figure reproduced by kind permission of Dr Steven Marsh, Anthony Nolan Research Institute, London, from the IPD-KIR database [www.ebi.ac.uk/ipd/kir/introduction.html]).