Selecting donor/recipient pairs with donor-versus-recipient NK alloreactivity. All persons possess the KIR2DL2 and/or KIR2DL3 receptors for HLA-C group 1 alleles. If they have HLA-C group 1 allele(s) in their HLA type, they possess HLA-C1-specific NK cells, which are alloreactive against cells from persons who do not express HLA-C group 1 alleles (top panel). A total of 97% of persons possess the KIR2DL1 receptor for HLA-C group 2. If they possess HLA-C group 2 allele(s) in their HLA type, they have HLA-C2-specific NK cells, which mediate alloreactions against cells from persons who do not express HLA-C group 2 alleles (middle panel). In one study on a large cohort,⁴¹  functional analyses detected alloreactivity when NK clones were tested against HLA-C group mismatched allogeneic targets. Frequencies of alloreactive NK clones were high, that is, 8 ± 6 cells in 100 (mean ± SD) for HLA-C group 2 mismatches; 5 ± 3 cells in 100 for group 1 mismatches. Finally (bottom panel), 90% of persons possess the KIR3DL1 receptor for HLA-Bw4 alleles. When they have HLA-Bw4 allele(s) in their HLA type, they may have HLA-Bw4–specific NK cells that are alloreactive against Bw4-negative cells. When NK clones from HLA-Bw4–positive persons who possessed the KIR3DL1 gene were tested against allogeneic HLA-Bw4–negative targets, alloreactive NK clones were detected in 2 of 3 persons.⁴¹  Reprinted from Velardi (Role of KIRs and KIR ligands in hematopoietic transplantation. Curr Opin Immunol. 2008;20:581-587) with permission.