Recombinant adenovirus coexpressing covalent peptide/MHC class II complex and B7-1: In vitro and in vivo activation of myelin basic protein-specific T cells
Recombinant adenovirus coexpressing covalent peptide/MHC class II complex and B7-1: In vitro and in vivo activation of myelin basic protein-specific T cells
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DOI：
10.4049/jimmunol.167.3.1297
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发表时间：
2001-08-01
影响因子：
4.4
通讯作者：
Li, W
中科院分区：
文献类型：
--
作者：
Chen, J;Huber, BT;Li, W
先前的研究已经证明，具有与其β-链基因融合的抗原肽的MHC II类分子能够将该肽呈递给CD 4（+）T细胞。我们假设共价肽/II类复合物可以指导辅助分子以TCR引导的方式特异性地在T细胞上发挥其功能。为了验证这一假设，我们产生了几种表达共价髓鞘碱性蛋白肽/I-A（u）复合物（MBP 1 -11/I-A（u））和共刺激分子B7-1的重组腺病毒。功能研究表明，腺病毒感染的细胞能够激活MBP，ii-特异性T细胞杂交瘤。B7-1分子和MBP 1 -11/I-A（u）通过相同腺病毒的共表达导致由病毒感染的细胞引起的T细胞活化的协同作用。此外，在用各种腺病毒感染的同基因小鼠中的研究揭示，MBP 1 -11特异性T细胞在体内通过B7-1和MBP 1 -11/I-A（u）的共表达而特异性活化。总之，共价肽/II类复合物和辅助分子由相同的腺病毒的共表达提供了一种独特的策略，以调节表位特异性T细胞应答的TCR-引导的方式。这种方法可能适用于研究其他辅助分子在TCR II类分子的接合中的作用，通过在重组腺病毒中用其他辅助分子取代B7-1。
Previous studies have demonstrated that an MHC class Il molecule with an antigenic peptide genetically fused to its beta -chain is capable of presenting this peptide to CD4(+) T cells. We hypothesized that covalent peptide/class II complex may direct the accessory molecules to exert their function specifically onto T cells in a TCR-guided fashion. To test this hypothesis, we generated several recombinant adenoviruses expressing covalent myelin basic protein peptide/I-A(u) complex (MBP1-11/I-A(u)) and the costimulatory molecule B7-1. Functional studies demonstrated that adenovirus-infected cells are capable of activating an MBP,ii-specific T cell hybridoma. Coexpression of the B7-1 molecule and MBP1-11/I-A(u) by the same adenovirus leads to synergy in T cell activation elicited by virus-infected cells. Furthermore, studies in syngeneic mice infected with the various adenoviruses revealed that MBP1-11-specific T cells are specifically activated by the coexpression of B7-1 and MBP1-11/I-A(u) in vivo. In conclusion, the coexpression of the covalent peptide/class II complex and accessory molecules by the same adenovirus provides a unique strategy to modulate the epitope-specific T cell response in a TCR-guided fashion. This approach may be applicable to investigate the roles of other accessory molecules in the engagement of the TCR class II molecule by substituting B7-1 with other accessory molecules in the recombinant adenovirus.