Distribution of human killer cell immunoglobulin-like receptors and ligands among blood donors of Catalonia.

ABSTRACT

Killer cell immunoglobulin-like receptors (KIR) belong to a diverse family of receptors present in NK cells and certain subsets of T cells. They bind to HLA class I molecules and, such as these, are highly polymorphic. This study is the first to determine KIR gene content diversity and perform high-resolution genotyping of corresponding HLA class I ligands in 445 unrelated blood donors resident in Catalonia (northeast Spanish region) and registered in the Blood and Tissue Bank of Barcelona between 2017 and 2018. The study was performed using a new next-generation sequencing method developed and validated by our group, with an important hands-on-time reduction and very cost-effectiveness. Thirty-eight KIR genotypes were observed. Haplotype combination frequencies were 24.49% for AA, 75.51% for BX. The most frequent genotype, found in 109 individuals (24.49%), was genotype ID 1. Seventeen genotypes occurred only once. Thirty individuals carried all KIR genes (genotype ID 6). We detected 46 HLA-A, 63 HLA-A-B, and 40 HLA-A-C alleles. A majority of individuals were heterozygous for C1/C2 (42.24%), 38.43% were homozygous for C1, and 19.33% were homozygous for C2. The most common KIR-HLA ligand pair was KIR3DL1-Bw4+, present in 75.73% of cases. No differences were found in KIR gene frequencies between the Catalan cohort and other Iberian Peninsula populations. Our findings will be useful for guiding further research evaluating the functional significance of KIR-ligand associations in specific diseases.