Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function.
Comparative analysis of B7-1 and B7-2 costimulatory ligands: expression and function.
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B7-1和B7-2共刺激配体的比较分析：表达和功能。
DOI：
10.1084/jem.180.2.631
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发表时间：
1994-08-01
期刊：
影响因子：
--
通讯作者：
Hodes RJ
中科院分区：
文献类型：
--
作者：
Hathcock KS;Laszlo G;Pucillo C;Linsley P;Hodes RJ
抗原特异性T细胞活化需要T细胞受体（TCR）与抗原结合，以及适当的共刺激分子的参与。被最广泛研究的共刺激途径是T细胞上的CD28和CTLA4与抗原呈递细胞上的B7（现称为B7 - 1）之间的相互作用。最近，描述了CTLA4的第二种共刺激配体B7 - 2，这表明了共刺激相互作用的潜在复杂性。本报告研究并比较了B7 - 1和B7 - 2的表达及功能。总体而言，这些结果表明：（a）B7 - 1和B7 - 2可由多种细胞类型表达，包括B细胞、T细胞、巨噬细胞和树突状细胞，因此所有这些细胞都是传递由这些分子介导的共刺激信号的候选群体；（b）用脂多糖（LPS）或抗IgD - 葡聚糖刺激B细胞可诱导B7 - 1和B7 - 2的表达，并且两种共刺激分子在培养18 - 42小时后达到表达峰值。在刺激后所检测的所有时间点，这些B细胞群上B7 - 2的表达都显著高于B7 - 1的表达；（c）阻断B7 - 2的共刺激活性可抑制TCR依赖性T细胞增殖和细胞因子产生，但不影响TCR信号传导的早期结果，如CD69或白细胞介素2受体α（IL - 2Rα）的诱导；（d）B7 - 1和B7 - 2的表达可受多种刺激调节。此外，B7 - 1和B7 - 2的表达可由同一刺激独立调节，这为调节共刺激以及免疫应答的机制增加了额外的复杂性。
Antigen-specific T cell activation requires the engagement of the T cell receptor (TCR) with antigen as well as the engagement of appropriate costimulatory molecules. The most extensively characterized pathway of costimulation has been that involving the interaction of CD28 and CTLA4 on the T cell with B7 (now termed B7-1) on antigen presenting cells. Recently, B7-2 a second costimulatory ligand for CTLA4, was described, demonstrating the potential complexity of costimulatory interactions. This report examines and compares the expression and function of B7-1 and B7-2. Overall these results indicate that (a) B7-1 and B7-2 can be expressed by multiple cell types, including B cells, T cells, macrophages, and dendritic cells, all of which are therefore candidate populations for delivering costimulatory signals mediated by these molecules; (b) stimulating B cells with either LPS or anti-IgD-dextran induced expression of both B7- 1 and B7-2, and peak expression of both costimulatory molecules occurred after 18-42 h of culture. Expression of B7-2 on these B cell populations was significantly higher than expression of B7-1 at all times assayed after stimulation; (c) blocking of B7-2 costimulatory activity inhibited TCR-dependent T cell proliferation and cytokine production, without affecting early consequences of TCR signaling such as induction of CD69 or interleukin 2 receptor alpha (IL-2R alpha); and (d) expression of B7-1 and of B7-2 can be regulated by a variety of stimuli. Moreover, expression of B7-1 and B7-2 can be independently regulated by the same stimulus, providing an additional complexity in the mechanisms available for regulating costimulation and hence immune response.