CTLA-4 is a second receptor for the B cell activation antigen B7.
CTLA-4 is a second receptor for the B cell activation antigen B7.
复制标题
DOI：
10.1084/jem.174.3.561
复制
发表时间：
1991-09-01
影响因子：
15.3
通讯作者：
Ledbetter, J A
中科院分区：
文献类型：
--
作者：
Linsley, P S;Brady, W;Urnes, M;Grosmaire, L S;Damle, N K;Ledbetter, J A
T和B淋巴细胞之间的功能相互作用是免疫反应最佳激活所必需的。最近，T淋巴细胞受体CD28被证明与活化的B淋巴细胞上的B7受体结合，从而协同刺激IL-2的产生和T细胞的增殖。CTLA-4是一种来自细胞毒性T细胞的膜受体，与CD28同源，其基因与CD28基因位于同一染色体带上。然而，目前尚不清楚CD28和CTLA-4是否也具有相同的功能特性。为了研究CTLA-4的功能特性，我们在CTLA-4的胞外区和免疫球蛋白C伽马链之间进行了可溶性基因融合。在这里，我们发现由该构建体编码的融合蛋白CTLA4Ig与B7转基因的中国仓鼠卵巢细胞和淋巴母细胞特异性结合。CTLA4Ig还从细胞表面125I标记的这些细胞的提取物中免疫沉淀B7。测定了125I标记的B7Ig融合蛋白与固定化CTLA4Ig的亲和力(Kd值约为12 nM)。最后，我们证明CTLA4Ig是一种依赖于T和B淋巴细胞之间的细胞相互作用的体外免疫反应的有效抑制物。这些发现提供了直接的证据，证明CTLA-4与其结构上的同系物CD28一样，能够与活化的B细胞上的B7受体结合。涉及B7受体的淋巴细胞相互作用在体外同种异体抗原反应中具有重要的功能。
Functional interactions between T and B lymphocytes are necessary for optimal activation of an immune response. Recently, the T lymphocyte receptor CD28 was shown to bind the B7 counter-receptor on activated B lymphocytes, and subsequently to costimulate interleukin 2 production and T cell proliferation. CTLA-4 is a predicted membrane receptor from cytotoxic T cells that is homologous to CD28 and whose gene maps to the same chromosomal band as the gene for CD28. It is not known, however, if CD28 and CTLA-4 also share functional properties. To investigate functional properties of CTLA-4, we have produced a soluble genetic fusion between the extracellular domain of CTLA-4 and an immunoglobulin C gamma chain. Here, we show that the fusion protein encoded by this construct, CTLA4Ig, bound specifically to B7-transfected Chinese hamster ovary cells and to lymphoblastoid cells. CTLA4Ig also immunoprecipitated B7 from cell surface 125I-labeled extracts of these cells. The avidity of 125I-labeled B7Ig fusion protein for immobilized CTLA4Ig was estimated (Kd approximately 12 nM). Finally, we show that CTLA4Ig was a potent inhibitor of in vitro immune responses dependent upon cellular interactions between T and B lymphocytes. These findings provide direct evidence that, like its structural homologue CD28, CTLA- 4 is able to bind the B7 counter-receptor on activated B cells. Lymphocyte interactions involving the B7 counter-receptor are functionally important for alloantigen responses in vitro.