Structure of murine CTLA-4 and its role in modulating T cell responsiveness
Structure of murine CTLA-4 and its role in modulating T cell responsiveness
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DOI：
10.1126/science.290.5492.816
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发表时间：
2000-10-27
期刊：
影响因子：
56.9
通讯作者：
Nathenson, SG
中科院分区：
文献类型：
--
作者：
Ostrov, DA;Shi, WX;Nathenson, SG
T细胞应答的有效调节依赖于通过两种相关的细胞表面受体CD 28和细胞毒性T淋巴细胞相关抗原4（CTLA-4）传递的相反信号。CTLA-4的二聚化是与B7配体形成高亲合力复合物和传递减弱T细胞活化的信号所必需的。我们测定了CTLA-4细胞外部分的晶体结构，分辨率为2.0埃。CTLA-4属于免疫球蛋白超家族，具有与Vor结构域相似的链拓扑结构，具有不寻常的二聚化模式，将B7结合位点置于二聚化界面的远端。这种组织允许每个CTLA-4二聚体结合两个二价B7分子，并表明这些组分在免疫突触内的周期性排列可能有助于调节T细胞反应性。
The effective regulation of T cell responses is dependent on opposing signals transmitted through two related cell-surface receptors, CD28 and cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4). Dimerization of CTLA-4 is required for the formation of high-avidity complexes with B7 ligands and for transmission of signals that attenuate T cell activation. We determined the crystal structure of the extracellular portion of CTLA-4 to 2.0 angstrom resolution. CTLA-4 belongs to the immunoglobulin superfamily and displays a strand topology similar to Vor domains, with an unusual mode of dimerization that places the B7 binding sites distal to the dimerization interface. This organization allows each CTLA-4 dimer to bind two bivalent B7 molecules and suggests that a periodic arrangement of these components within the immunological synapse may contribute to the regulation of T cell responsiveness.