The vav exchange factor is an essential regulator in actin-dependent receptor translocation to the lymphocyte-antigen-presenting cell interface
The vav exchange factor is an essential regulator in actin-dependent receptor translocation to the lymphocyte-antigen-presenting cell interface
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DOI：
10.1073/pnas.97.18.10150
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发表时间：
2000-08-29
影响因子：
11.1
通讯作者：
Davis, MM
中科院分区：
文献类型：
--
作者：
Wülfing, C;Bauch, A;Davis, MM
在T细胞与抗原呈递细胞（APC）的相互作用期间，包括T细胞受体（TCR）/主要组织相容性复合物（MHC）在内的几种受体配体对以限定的几何图案在T细胞/APC界面处积累。这种积累依赖于T细胞皮层肌动蛋白细胞骨架向界面的运动。在这里，我们研究的鸟嘌呤核苷酸交换因子vav在这一过程中的参与。我们将129只vav（-/-）小鼠与B10/BR 5C.C7 TCR转基因小鼠杂交，用负载肽的APC刺激子代T细胞，发现这些vav（+/-）小鼠的TCR/MHC在T细胞/APC界面的聚集和T细胞肌动蛋白细胞骨架重排明显缺陷，还观察到来自非TCR转基因129小鼠的T细胞的超抗原介导的T细胞活化的类似缺陷，尽管在这种情况下，其在vav（-/-）小鼠中更明显，这些数据表明，vav是T细胞活化过程中细胞骨架重排的重要调节因子。
During the interaction of a T cell with an antigen-presenting cell (APC), several receptor ligand pairs, including the T cell receptor (TCR)/major histocompatibility complex (MHC), accumulate at the T cell/APC interface in defined geometrical patterns. This accumulation depends on a movement of the T cell cortical actin cytoskeleton toward the interface. Here we study the involvement of the guanine nucleotide exchange factor vav in this process. We crossed 129 vav(-/-) mice with B10/BR 5C.C7 TCR transgenic mice and used peptide-loaded APCs to stimulate T cells from the offspring, We found that the accumulation of TCR/MHC at the T cell/APC interface and the T cell actin cytoskeleton rearrangement were clearly defective in these vav(+/-) mice, A comparable defect in superantigen-mediated T cell activation of T cells from non-TCR transgenic 129 mice was also observed, although in this case it was more apparent in vav(-/-) mice, These data indicate that vav is an essential regulator of cytoskeletal rearrangements during T cell activation.