Activating killer cell immunoglobulin-like receptor 2DS2 binds to HLA-A*11
Activating killer cell immunoglobulin-like receptor 2DS2 binds to HLA-A*11
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DOI：
10.1073/pnas.1322052111
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发表时间：
2014-02-18
影响因子：
11.1
通讯作者：
Ren, Ee Chee
中科院分区：
文献类型：
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作者：
Liu, Jingxian;Xiao, Ziwei;Ren, Ee Chee
抑制性杀伤细胞免疫球蛋白样受体(KIRS)主要识别人类白细胞抗原C(HLAC)和人类白细胞抗原(Bw4)的配体，但对KIRS的配体知之甚少。我们在此报告了激活KIR 2DS2的同源配体为人类白细胞抗原-A*11：01。KIR2DS2-HLA-A*11：01复合物的晶体结构在2.5埃分辨率下得到解析，揭示了与抑制性KIR不同的残基结合特征，以及Tyr45和Asp72残基在形成与HLA-A*11：01结合特异性中的关键作用。利用KIR2DS2四聚体，证实了活细胞表面的HLA-A*11：01的结合，并且这种结合可以通过肽的p8位残基的变化来改变，这表明了肽序列对KIR-HLA结合的影响。此外，还利用异核单量子相干核磁共振技术绘制了KIR与HLA界面上的关键残基参与的情况，验证了晶体结构中观察到的数据。我们的数据为激活KIR2DS2识别A*11：01提供了结构证据，并扩展了我们对KIR-HLA结合光谱的理解。
Inhibitory killer cell Ig-like receptors (KIRs) are known to recognize HLA ligands mainly of the HLA-C and Bw4 groups, but the ligands for KIRs are poorly understood. We report here the identification of the cognate ligand for the activating KIR 2DS2 as HLA-A*11:01. The crystal structure of the KIR2DS2-HLA-A*11:01 complex was solved at 2.5-angstrom resolution and revealed residue-binding characteristics distinct from those of inhibitory KIRs with HLA-C and the critical role of residues Tyr45 and Asp72 in shaping binding specificity to HLA-A*11: 01. Using KIR2DS2 tetramers, binding to surface HLA-A*11: 01 on live cells was demonstrated and, furthermore, that binding can be altered by residue changes at p8 of the peptide, indicating the influence of peptide sequence on KIR-HLA association. In addition, heteronuclear single quantum coherence NMR was used to map the involvement of critical residues in HLA binding at the interface of KIR and HLA, and validates the data observed in the crystal structure. Our data provide structural evidence of the recognition of A*11:01 by the activating KIR2DS2 and extend our understanding of the KIR-HLA binding spectrum.