Rosner Cornelia, Kruse Philip H, Hermes Meike, Otto Nicole, Walter Lutz
Primate Genetics Laboratory, German Primate Center-Leibniz Institute for Primate Research, 37077 Göttingen, Germany.
J Immunol. 2011 Feb 15;186(4):2156-63. doi: 10.4049/jimmunol.1002634. Epub 2011 Jan 21.
Specific interactions between killer cell Ig-like receptors (KIRs) and MHC class I ligands have not been described in rhesus macaques despite their importance in biomedical research. Using KIR-Fc fusion proteins, we detected specific interactions for three inhibitory KIRs (3DLW03, 3DL05, 3DL11) and one activating KIR (3DS05). As ligands we identified Macaca mulatta MHC (Mamu)-A1- and Mamu-A3-encoded allotypes, among them Mamu-A1001:01, which is well known for association with slow progression to AIDS in the rhesus macaque experimental SIV infection model. Interactions with Mamu-B or Mamu-I molecules were not found. KIR3DLW03 and KIR3DL05 differ in their binding sites to their shared ligand Mamu-A1001:01, with 3DLW03 depending on presence of the α1 domain, whereas 3DL05 depends on both the α1 and α2 domains. Fine-mapping studies revealed that binding of KIR3DLW03 is influenced by presence of the complete Bw4 epitope (positions 77, 80-83), whereas that of KIR3DL05 is mainly influenced by amino acid position 77 of Bw4 and positions 80-83 of Bw6. Our findings allowed the successful prediction of a further ligand of KIR3DL05, Mamu-A1*002:01. These functional differences of rhesus macaque KIR3DL molecules are in line with the known genetic diversification of lineage II KIRs in macaques.
尽管杀伤细胞免疫球蛋白样受体（KIR）与MHC I类配体之间的特异性相互作用在生物医学研究中具有重要意义，但在恒河猴中尚未见报道。我们利用KIR-Fc融合蛋白，检测到三种抑制性KIR（3DLW03、3DL05、3DL11）和一种激活性KIR（3DS05）的特异性相互作用。作为配体，我们鉴定出恒河猴MHC（Mamu）-A1和Mamu-A3编码的同种异型，其中Mamu-A1001:01在恒河猴实验性SIV感染模型中因与艾滋病进展缓慢相关而闻名。未发现与Mamu-B或Mamu-I分子的相互作用。KIR3DLW03和KIR3DL05与其共同配体Mamu-A1001:01的结合位点不同，3DLW03依赖于α1结构域的存在，而3DL05则依赖于α1和α2结构域。精细定位研究表明，KIR3DLW03的结合受完整Bw4表位（第77、80 - 83位）存在的影响，而KIR3DL05的结合主要受Bw4的第77位氨基酸和Bw6的第80 - 83位氨基酸的影响。我们的研究结果成功预测了KIR3DL05的另一种配体Mamu-A1*002:01。恒河猴KIR3DL分子的这些功能差异与猕猴中已知的II类KIR基因多样化一致。
