Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses
Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses
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DOI：
10.1016/j.immuni.2007.05.016
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发表时间：
2007-07-01
期刊：
影响因子：
32.4
通讯作者：
Freeman, Gordon J.
中科院分区：
文献类型：
--
作者：
Butte, Manish J.;Keir, Mary E.;Freeman, Gordon J.
共刺激分子B7：CD28家族中的通路调节T细胞的激活和耐受。CD28(-/-)CTLA4(-/-)T细胞的B7依赖反应以及对程序性死亡-1配体1或2分子(PD-L1或PD-L2)的刺激和抑制功能的报道表明，这137个家族成员有额外的受体。我们发现B7-1和PD-L1与B7-1：CD28和B7-1：CTLA-4的亲和力居中。PD-L1：B7-1接口与B7-1：CTLA-4和PD-L1：PD-1(程序性死亡-1)接口重叠。B7-1与PD-L1的相互作用抑制T细胞活化和细胞因子的产生。PD-1缺陷与PD-1、B7-1双缺陷T细胞对PD-L1的反应以及CD28、CTLA-4双缺陷与CD28、CTLA-4、PD-L1三缺陷T细胞对B7-1的反应表明PD-L1和B7-1特异性地相互作用以抑制T细胞的激活。我们的发现指出，B7-1和PD-L1之间存在实质性的双向抑制相互作用，并为B7：CD28家族的免疫调节功能增加了一个额外的维度。
Pathways in the B7:CD28 family of costimulatory molecules regulate T cell activation and tolerance. B7-dependent responses in Cd28(-/-) Ctla4(-/-) T cells together with reports of stimulatory and inhibitory functions for Programmed Death-1 Ligand 1 or 2 molecules (PD-L1 or PD-L2) have suggested additional receptors for these 137 family members. We show that B7-1 and PD-L1 interacted with affinity intermediate to that of B7-1:CD28 and B7-1:CTLA-4. The PD-L1:B7-1 interface overlapped with the B7-1:CTLA-4 and PD-L1:PD-1 (Programmed Death-1) interfaces. T cell activation and cytokine production were inhibited by the interaction of B7-1 with PD-L1. The responses of PD-1 -deficient versus PD-1,B7-1 double-deficient T cells to PD-L1 and of CD28,CTLA-4 double-deficient versus CD28,CTLA-4,PD-L1 triple-deficient T cells to B7-1 demonstrated that PD-L1 and B7-1 interact specifically to inhibit T cell activation. Our findings point to a substantial bidirectional inhibitory interaction between B7-1 and PD-L1 and add an additional dimension to immunoregulatory functions of the B7:CD28 family.