KIR3DL01 recognition of Bw4 ligands in the rhesus macaque: maintenance of Bw4 specificity since the divergence of apes and Old World monkeys.

KIR3DL01 recognition of Bw4 ligands in the rhesus macaque: maintenance of Bw4 specificity since the divergence of apes and Old World monkeys.
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DOI:
10.4049/jimmunol.1302883
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发表时间:
2014-02-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Evans DT
Evans DT
中科院分区:
其他
文献类型:
--
作者:
Schafer JL;Colantonio AD;Neidermyer WJ;Dudley DM;Connole M;O'Connor DH;Evans DT

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恒河猴KIR的MHC I类配体的鉴定对于我们对KIR和MHC I类共同进化的基本理解以及在这种非人灵长类动物模型中研究用于AIDS和其他病毒性疾病的NK细胞应答是至关重要的。在这里,我们表明,Mamu-KIR 3DL 01,这是由大约90%的恒河猴表达,识别MHC I类分子与Bw 4基序。表达Mamu-KIR 3DL 01的原代NK细胞通过用本文的mAb染色来鉴定,所述mAb显示结合在位置233处具有天冬氨酸的Mamu-KIR 3DL 01同种异型。表达Bw 4分子Mamu-B *007:01、-B*041:01、-B*058:02和-B*065:01的细胞系抑制了Mamu-KIR 3 DL 01 + NK细胞的细胞溶解活性。Bw 4基序是Mamu-KIR 3DL 01识别所必需的,因为该区域中的取代消除了Mamu-KIR 3DL 01 + NK细胞抑制。然而,Bw 4基序的存在不足以识别,因为另一种Bw 4分子Mamu-B*017:01未能抑制这些NK细胞的细胞溶解活性。基于人KIR 3DL 1-HLA-Bw 4复合物的三维结构预测为KIR接触的Mamu-B*017:01中的三个残基用其他Mamu-Bw 4配体在这些位置处的相应残基替换恢复了Mamu-KIR 3DL 01 + NK细胞抑制。这些结果定义了恒河猴中最多态和最常表达的KIR之一的配体特异性,并揭示了Mamu-KIR 3DL 01和人KIR 3DL 1在Bw 4识别中的相似性,尽管这两个KIR之间不存在正向同源关系或预测与MHC I类配体相互作用的表面残基的保守性。
The identification of MHC class I ligands for rhesus macaque KIRs is fundamental to our basic understanding of KIR and MHC class I co-evolution and to the study of NK cell responses in this non-human primate model for AIDS and other viral diseases. Here we show that Mamu-KIR3DL01, which is expressed by approximately 90% of rhesus macaques, recognizes MHC class I molecules with a Bw4 motif. Primary NK cells expressing Mamu-KIR3DL01 were identified by staining with a mAb herein shown to bind Mamu-KIR3DL01 allotypes with an aspartic acid at position 233. The cytolytic activity of Mamu-KIR3DL01+ NK cells was suppressed by cell lines expressing the Bw4 molecules Mamu-B*007:01, -B*041:01, -B*058:02, and -B*065:01. The Bw4 motif was necessary for Mamu-KIR3DL01 recognition, since substitutions in this region abrogated Mamu-KIR3DL01+ NK cell inhibition. However, the presence of a Bw4 motif was not sufficient for recognition, since another Bw4 molecule, Mamu-B*017:01, failed to suppress the cytolytic activity of these NK cells. Replacement of three residues in Mamu-B*017:01, predicted to be KIR-contacts based on the 3-dimensional structure of the human KIR3DL1-HLA-Bw4 complex, with the corresponding residues at these positions for the other Mamu-Bw4 ligands restored Mamu-KIR3DL01+ NK cell inhibition. These results define the ligand specificity of one of the most polymorphic and commonly expressed KIRs in the rhesus macaque, and reveal similarities in Bw4 recognition by Mamu-KIR3DL01 and human KIR3DL1, despite the absence of an orthologous relationship between these two KIRs or conservation of surface residues predicted to interact with MHC class I ligands.
长臂猿中 MHC-C 和 MHC-G 的缺失伴随着一个小的、可变的和不规则的杀伤细胞 Ig 样受体位点。
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影响因子: --
作者:
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