Activating receptor KIR2DS2 bound to HLA-C1 reveals the novel recognition features of activating receptor
Activating receptor KIR2DS2 bound to HLA-C1 reveals the novel recognition features of activating receptor
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DOI：
10.1111/imm.13439
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发表时间：
2022-01-11
期刊：
影响因子：
6.4
通讯作者：
Yin，Lei
中科院分区：
文献类型：
--
作者：
Yang，Yi;Bai，Hua;Yin，Lei
杀伤细胞免疫球蛋白样受体(KIRS)是调节病毒感染或自然杀伤(NK)细胞杀伤癌细胞的重要受体。KIR2DS2可以识别来自丙型肝炎病毒或全球黄病毒(如登革热和寨卡病毒)的多肽来激活NK细胞，并在癌症免疫治疗中显示出良好的效果。在这里，我们介绍了KIR2DS2和人类白细胞抗原-C*0102的复杂结构，分辨率为2.5？我们的结构表明KIR2DS2可以与人类白细胞抗原C*0102和人类白细胞抗原A*1101以两种不同的方向结合。此外，Tyr45(在激活受体KIR2DS2中)和Phe45(在抑制KIRS中)区分了激活KIRS和抑制KIRS之间两种不同的结合模式和结合亲和力。多肽保守的‘AT’基序介导识别，并决定识别的多肽特异性。这些结构特征揭示了KIR如何激活NK细胞，并为NK细胞的免疫治疗提供了分子基础。
Killer cell immunoglobulin‐like receptors (KIRs) are important receptors for regulating the killing of virus‐infected or cancer cells of natural killer (NK) cells. KIR2DS2 can recognize peptides derived from hepatitis C virus (HCV) or global flaviviruses (such as dengue and Zika) presented by HLA‐C*0102 to activate NK cells, and has shown promising results when used for cancer immunotherapy. Here, we present the complex structure of KIR2DS2 with HLA‐C*0102 at a resolution of 2·5Å. Our structure reveals that KIR2DS2 can bind with HLA‐C*0102 and HLA‐A*1101 in two different directions. Moreover, Tyr45 (in activating receptor KIR2DS2) and Phe45 (in inhibitory KIRs) distinguish the two different binding models and binding affinity between activating KIRs and inhibitory KIRs. The conserved ‘AT’ motif of the peptide mediates recognition and determines the peptide specificity of recognition. These structural characteristics shed light on how KIRs activate NK cells and can provide a molecular basis for immunotherapy by NK cells.