Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical

Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical
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DOI:
10.1016/s1074-7613(00)80080-1
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发表时间:
1999-07-01
期刊:
影响因子:
32.4
通讯作者:
Wiley, DC
Wiley, DC
中科院分区:
医学1区
文献类型:
--
作者:
Ding, YH;Baker, BM;Wiley, DC

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利用T细胞实验、动力学和热力学测量以及x射线晶体学研究了HTLV-1 Tax肽与HLA-A2结合的三种单取代肽变体与A6 T细胞受体的相互作用。这三种肽/MHC配体包括对TCR具有不同亲和力的弱激动剂和拮抗剂。三种A6-TCR/肽/HLA-A2复合物的三维结构彼此之间以及与野生型激动剂复合物非常相似,在界面处进行了微小的调整以适应肽取代(P6A, V7R和Y8A)。结构变化与诱导的T细胞信号类型之间缺乏相关性,这为α - β TCR中不同配体诱导的构象变化不会产生不同的信号提供了直接证据。
The interactions of three singly substituted peptide variants of the HTLV-1 Tax peptide bound to HLA-A2 with the A6 T cell receptor have been studied using T cell assays, kinetic and thermodynamic measurements, and X-ray crystallography. The three peptide/MHC ligands include weak agonists and antagonists with different affinities for TCR. The three-dimensional structures of the three A6-TCR/peptide/HLA-A2 complexes are remarkably similar to each other and to the wild-type agonist complex, with minor adjustments at the interface to accommodate the peptide substitutions (P6A, V7R, and Y8A). The lack of correlation between structural changes and the type of T cell signals induced provides direct evidence that different signals are not generated by different ligand-induced conformational changes in the alpha beta TCR.