- HLA molecules carrying the epitope for ligand of KIR (HLA-B-Bw4, HLA-C1, HLA-C2) are indicated as ○. HLA-homo-iPSC lines of these four haplotypes have been supplied by CiRA Foundation. The allotype frequency of HLA-C1 versus C2 in the Japanese population is 92.7:7.3. When the regenerated tissues from these HLA-homo-iPSCs are transplanted into HLA-hetero recipients, one allele of the recipient must be matched to the HLA-homo iPSCs. As all top 4 HLA haplotype frequencies have the C1 epitope, recipients should have at least a C1 epitope on one allele. On the other hand, because the haplotype of the other allele will be randomly selected, the probability that the recipient has the C1/C1 genotype is 7.3%, because it should be equal to the allotype frequency of the C2 type. The allotype frequency of B-Bw4 in HLA-B is known to be about 30%. A KIR-ligand mismatch will occur when HLA-homo grafts lacking a B-Bw4 ligand are transplanted into an HLA-hetero recipient carrying B-Bw4. Therefore, in the first 2 cases, a B-Bw4 mismatch will not take place. In case of no. 3 and no. 4, one allele of the recipient should be B-Bw-4 negative, because one allele should be the same as the no. 3 or no. 4 haplotype. Because the other haplotype of the recipient is randomly selected, the probability that the recipient has B-Bw4 is the same as the B-Bw4 allotype frequency (30% among Japanese). Thus, in the no. 3 or no. 4 case, the B-Bw4 mismatch occurs with 30% frequency. As the KIR-ligand mismatch regarding C1/C2 or Bw4 takes place in an independent manner, the frequency of KIR-ligand mismatch of at least one mismatch in nos. 3 and 4 case is estimated to be about 35% calculated as [1 − (1 − 0.073) × (1 − 0.3) = 0.3511].
