Closa Laia, Vidal Francisco, Herrero Maria J, Caro Jose L
Histocompatibility and Immunogenetics Laboratory, Blood and Tissue Bank, Barcelona, Spain.
Department of Immunology, Hospital Clínic, Transfusional Medicine Group, Vall d'Hebron Research Institute, Autonomous University of Barcelona (VHIR-UAB), Barcelona, Spain.
HLA. 2020 Mar;95(3):179-188. doi: 10.1111/tan.13754. Epub 2019 Nov 25.
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.
杀伤细胞免疫球蛋白样受体（KIR）属于存在于自然杀伤细胞（NK细胞）和某些T细胞亚群中的多种受体家族。它们与I类人类白细胞抗原（HLA）分子结合，并且像这些分子一样具有高度多态性。本研究首次确定了445名居住在加泰罗尼亚（西班牙东北部地区）且于2017年至2018年在巴塞罗那血液与组织库登记的无关献血者的KIR基因含量多样性，并对相应的I类HLA配体进行了高分辨率基因分型。该研究使用了我们团队开发并验证的新一代测序新方法，显著减少了实际操作时间且极具成本效益。观察到38种KIR基因型。单倍型组合频率为：AA型占24.49%，BX型占75.51%。最常见的基因型是ID 1型，在109名个体中出现（占24.49%）。17种基因型仅出现一次。30名个体携带所有KIR基因（基因型ID 6）。我们检测到46个HLA - A、63个HLA - A - B和40个HLA - A - C等位基因。大多数个体C1/C2为杂合子（42.24%），38.43%为C1纯合子，19.33%为C2纯合子。最常见的KIR - HLA配体对是KIR3DL1 - Bw4 +，在75.73%的病例中存在。加泰罗尼亚队列与伊比利亚半岛其他人群之间的KIR基因频率未发现差异。我们的研究结果将有助于指导进一步研究，评估KIR - 配体关联在特定疾病中的功能意义。
