Peptide-Major Histocompatibility Complex Dimensions Control Proximal Kinase-Phosphatase Balance during T Cell Activation
Peptide-Major Histocompatibility Complex Dimensions Control Proximal Kinase-Phosphatase Balance during T Cell Activation
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DOI：
10.1074/jbc.m109.039966
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发表时间：
2009-09-18
影响因子：
4.8
通讯作者：
van der Merwe, P. Anton
中科院分区：
文献类型：
--
作者：
Choudhuri, Kaushik;Parker, Mathew;van der Merwe, P. Anton
T细胞抗原识别需要T细胞受体（TCR）与肽抗原和主要组织相容性复合物分子（pMHC）之间的复合物结合，并且这种识别发生在T细胞和抗原呈递细胞之间的界面处。TCR和pMHC分子与其他丰富的细胞表面分子相比是小的，并且已经表明小尺寸在功能上是重要的。我们在这里表明，延长的小鼠和人的MHC I类分子废除T细胞抗原识别细胞因子的产生和靶细胞杀伤。这种延伸破坏了接触区的酪氨酸磷酸化和Zap70募集，而不影响TCR或辅助受体结合。与pMHC的延长形式的接触面积显示膜间距的增加和从大的酪氨酸磷酸酶CD 45的CD 3的分离效率较低。这些发现表明T细胞抗原识别强烈依赖于pMHC大小，并且与TCR触发需要TCR的分离或机械牵拉的模型一致。
T cell antigen recognition requires binding of the T cell receptor (TCR) to a complex between peptide antigen and major histocompatibility complex molecules (pMHC), and this recognition occurs at the interface between the T cell and the antigen-presenting cell. The TCR and pMHC molecules are small compared with other abundant cell surface molecules, and it has been suggested that small size is functionally important. We show here that elongation of both mouse and human MHC class I molecules abrogates T cell antigen recognition as measured by cytokine production and target cell killing. This elongation disrupted tyrosine phosphorylation and Zap70 recruitment at the contact region without affecting TCR or coreceptor binding. Contact areas with elongated forms of pMHC showed an increase in intermembrane distance and less efficient segregation of CD3 from the large tyrosine phosphatase CD45. These findings demonstrate that T cell antigen recognition is strongly dependent on pMHC size and are consistent with models of TCR triggering requiring segregation or mechanical pulling of the TCR.