Choudhuri Kaushik, Parker Mathew, Milicic Anita, Cole David K, Shaw Michael K, Sewell Andrew K, Stewart-Jones Guillaume, Dong Tao, Gould Keith G, van der Merwe P Anton
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
J Biol Chem. 2009 Sep 18;284(38):26096-105. doi: 10.1074/jbc.M109.039966. Epub 2009 Jul 23.
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.
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体分子（pMHC）之间的复合物结合，并且这种识别发生在T细胞与抗原呈递细胞之间的界面处。与其他丰富的细胞表面分子相比，TCR和pMHC分子较小，有人认为小尺寸在功能上很重要。我们在此表明，通过细胞因子产生和靶细胞杀伤来衡量，小鼠和人类MHC I类分子的延长均会消除T细胞抗原识别。这种延长破坏了接触区域的酪氨酸磷酸化和Zap70募集，而不影响TCR或共受体结合。与延长形式的pMHC的接触区域显示膜间距离增加，并且CD3与大酪氨酸磷酸酶CD45的分离效率降低。这些发现表明，T细胞抗原识别强烈依赖于pMHC大小，并且与需要TCR分离或机械拉动的TCR触发模型一致。
