B7-1 and B7-2: Similar costimulatory ligands with different biochemical, oligomeric and signaling properties

B7-1 and B7-2: Similar costimulatory ligands with different biochemical, oligomeric and signaling properties
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DOI:
10.1016/j.imlet.2005.11.019
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发表时间:
2006-04-15
期刊:
影响因子:
4.4
通讯作者:
Nathenson, SG
Nathenson, SG
中科院分区:
医学3区
文献类型:
--
作者:
Bhatia, S;Edidin, M;Nathenson, SG

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B7-1和B7-2是表达于抗原呈递细胞(APC)表面的同源共刺激配体。这些分子与T细胞共刺激受体CD 28和CTLA-4的结合对于T细胞免疫的活化和调节是必需的。尽管有很强的结构相似性,B7-1和B7-2表现出不同的生化特征,它们与共刺激受体的结合导致不同的T细胞功能结果。利用基于荧光共振能量转移(FRET)的光漂白,我们以前的研究已经证明B7-1和B7-2具有不同的细胞表面寡聚态。B7-1以二聚体形式存在,而B7-2以单体形式存在于细胞表面,这表明共刺激配体的独特细胞表面寡聚状态可能在调节T细胞应答中起关键作用。此外,据报道,树突状细胞中通过B7-1和B7-2的信号传导依赖于它们的同时表达,这提高了它们的直接相互作用或它们参与协同信号传导途径可能在抗原呈递细胞的功能中发挥作用的可能性。我们讨论了B7-1和B7-2的不同寡聚状态的生理相关性,并讨论了这些分子是否可以在细胞表面相互结合形成异源寡聚体。我们的研究结果表明,B7-1和B7-2不形成异源寡聚体,分别强调了B7-1和B7-2的二聚体和单体状态的生物学相关性。(C)2005 Elsevier B. V.保留所有权利。
B7-1 and B7-2 are homologous costimulatory ligands expressed on the surface of antigen presenting cells (APCs). Binding of these molecules to the T cell costimulatory receptors, CD28 and CTLA-4, is essential for the activation and regulation of T cell immunity. Despite strong structural similarities, B7-1 and B7-2 exhibit different biochemical features, and their binding to the costimulatory receptors results in distinct T cell functional outcomes. Using photobleaching based fluorescence resonance energy transfer (FRET), our previous studies have demonstrated that B7-1 and B7-2 have different cell surface oligomeric states. While B7-1 is present as a dimer, B7-2 exists as a monomer on the cell surface suggesting that the unique cell surface oligomeric states of the costimulatory ligands may play a key role in the regulation of T cell responses. Moreover, signaling via B7-1 and B7-2 in dendritic cells has been reported to be dependent on their simultaneous expression, raising the possibility that their direct interaction or their involvement in synergistic signaling pathways may play a role in the function of antigen presenting cells. We discuss physiological relevance of distinct oligomeric states of B7-1 and B7-2 and address whether these molecules can associate with one another on the cell surface to form hetero-oligomers. Our findings suggest that B7-1 and B7-2 do not form hetero-oligomers, underscoring the biological relevance of dimeric and monomeric state of B7-1 and B7-2, respectively. (C) 2005 Elsevier B.V. All rights reserved.