Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics
Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics
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DOI：
10.4049/jimmunol.174.5.2878
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发表时间：
2005-03-01
影响因子：
4.4
通讯作者：
Strong, RK
中科院分区：
文献类型：
--
作者：
Kaiser, BK;Barahmand-pour, F;Strong, RK
C型凝集素样免疫受体的NKG 2x/CD 94家族（x = A、B、C、E和H）通过识别特异性呈递源自Ia类前导序列的肽的MHC Ib类蛋白HLA-E来介导对在感染或肿瘤发生期间经常失调的MHC Ia类细胞表面表达的监视。在这项研究中，我们确定了三个NKG 2x/CD 94受体（NKG 2A，NKG 2C和NKG 2 E）和HLA-E与四个代表性肽的复合物之间的亲和力和相互作用热力学。抑制性NKG 2A/CD 94和活化性NKG 2 E/CD 94受体以不可区分的亲和力结合HLA-E，但亲和力显著高于活化性NKG 2C/CD 94受体。尽管存在微小的序列差异，但HLA-E呈递的肽显著影响亲和力; HLA-E等位基因差异没有影响。这些结果揭示了对驱动NK细胞效应器功能的相反激活和抑制信号的整合的重要限制。
The NKG2x/CD94 family of C-type lectin-like immunoreceptors (x = A, B, C, E, and H) mediates surveillance of MHC class Ia cell surface expression, often dysregulated during infection or tumorigenesis, by recognizing the MHC class Ib protein HLA-E that specifically presents peptides derived from class la leader sequences. In this study, we determine the affinities and interaction thermodynamics between three NKG2x/CD94 receptors (NKG2A, NKG2C, and NKG2E) and complexes of HLA-E with four representative peptides. Inhibitory NKG2A/CD94 and activating NKG2E/CD94 receptors bind HLA-E with indistinguishable affinities, but with significantly higher affinities than the activating NKG2C/CD94 receptor. Despite minor sequence differences, the peptide presented by HLA-E significantly influenced the affinities; HLA-E allelic differences had no effect. These results reveal important constraints on the integration of opposing activating and inhibitory signals driving NK cell effector functions.