KIR and HLA Genotyping

Between October 2016 and April 2019, 2.6 million donors recruited by DKMS were KIR genotyped at allelic resolution by DKMS Life Science Lab in Dresden, Germany, using next generation sequencing methods (53, 55, 56). Genotyping comprises the HLA loci HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1, the KIR loci KIR2DL1-5, KIR3DL1-3, KIR2DS1-5, KIR3DS1, KIR2DP1, and KIR3DP1, as well as ABO (57), RhD, CCR5 (58), and MIC-A/B (59). The KIR genotyping approach delivers both allele group information and copy numbers for every KIR gene (53). DNA was extracted from blood samples or buccal swabs with the informed consent of the donors.

For the analysis of KIR haplotypes, KIR genotyping results were shortened to the first three digits of the allele name, thereby merging alleles with synonymous substitutions within the coding region and non-coding mutations. Allelic ambiguities due to variations outside the typed exons (exons 3, 4, 5, 7, 8, and 9) were grouped and denoted by a trailing “c” (Supplementary Information S1). In the following, 3-digit allelic level and “c”-groups are referred to as “allele group” resolution. Since a clear distinction of genes of the loci KIR2DL5A and KIR2DL5B was not possible without sequence information on exon 1 and promoter region, we treated KIR2DL5A and KIR2DL5B as one locus. We considered 16 KIR loci in total.