Figure 3
Figure 3. Defining the optimal donor. Based on the KIR haplotype A that has a fixed gene content of 6 iKIRs and 1 aKIR, and the haplotype B that has a highly variable gene content and up to 5 aKIRs, donors can be assigned either to KIR genotype A/A (ie, homozygous for A haplotypes) or to B/x (having 1 or 2 B haplotypes). The Cen and Tel regions can reassemble to form recombinant haplotypes. Genetic association studies suggest that an optimal alloreactive donor will be one with an iKIR-KIRL mismatch and who possesses multiple aKIRs (haplotype B) next to iKIRs. The KIR B content score mainly reflects the number of aKIRs, and the highest score is associated with the highest number of aKIRs. NK cells from such donors with a high KIR B content score should, in principle, exert strong alloreactive antileukemic NK cell activity, and it has been shown that transplantation with donors homozygous for Cen KIR B haplotypes is associated with the lowest level of relapse and highest overall survival.36,42,43 The KIR B content score can easily be determined by KIR genotyping. Note that the majority of haplotype B donors do not express all genes shown in the figure.

Defining the optimal donor. Based on the KIR haplotype A that has a fixed gene content of 6 iKIRs and 1 aKIR, and the haplotype B that has a highly variable gene content and up to 5 aKIRs, donors can be assigned either to KIR genotype A/A (ie, homozygous for A haplotypes) or to B/x (having 1 or 2 B haplotypes). The Cen and Tel regions can reassemble to form recombinant haplotypes. Genetic association studies suggest that an optimal alloreactive donor will be one with an iKIR-KIRL mismatch and who possesses multiple aKIRs (haplotype B) next to iKIRs. The KIR B content score mainly reflects the number of aKIRs, and the highest score is associated with the highest number of aKIRs. NK cells from such donors with a high KIR B content score should, in principle, exert strong alloreactive antileukemic NK cell activity, and it has been shown that transplantation with donors homozygous for Cen KIR B haplotypes is associated with the lowest level of relapse and highest overall survival.36,42,43  The KIR B content score can easily be determined by KIR genotyping. Note that the majority of haplotype B donors do not express all genes shown in the figure.

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