Leupin O, Zaru R, Laroche T, Müller S, Valitutti S
BIL Research Center, Institute of Biochemistry, University of Lausanne, Epalinges, 1066, Switzerland.
Curr Biol. 2000 Mar 9;10(5):277-80. doi: 10.1016/s0960-9822(00)00362-6.
T lymphocytes are activated by the engagement of their antigen receptors (TCRs) with complexes of peptide and major histocompatibility complex (MHC) molecules displayed on the cell surface of antigen-presenting cells (APCs) [1]. An unresolved question of antigen recognition by T cells is how TCR triggering actually occurs at the cell-cell contact area. We visualized T-cell-APC contact sites using confocal microscopy and three-dimensional reconstruction of z-sections. We show the rapid formation of a specialized signaling domain at the T-cell-APC contact site that is characterized by a broad and sustained area of tyrosine phosphorylation. The T-lymphocyte cell-surface molecule CD2 is rapidly recruited into this signaling domain, whereas TCRs progressively percolate from the entire T-cell surface into the phosphorylation area. Remarkably, the highly expressed phosphatase CD45 is excluded from the signaling domain. Our results indicate that physiological TCR triggering at the T-cell-APC contact site is the result of a localized alteration in the balance between cellular kinases and phosphatases. We therefore provide experimental evidence to support current models of T-cell activation based on CD45 exclusion from the TCR signaling area [2] [3] [4].
T淋巴细胞通过其抗原受体（TCR）与抗原呈递细胞（APC）细胞表面展示的肽与主要组织相容性复合体（MHC）分子的复合物结合而被激活[1]。T细胞对抗原识别的一个尚未解决的问题是TCR触发在细胞间接触区域实际是如何发生的。我们使用共聚焦显微镜和z轴切片的三维重建来观察T细胞与APC的接触位点。我们展示了在T细胞与APC接触位点快速形成一个特殊的信号域，其特征是酪氨酸磷酸化的广泛且持续的区域。T淋巴细胞细胞表面分子CD2迅速被招募到这个信号域，而TCR则从整个T细胞表面逐渐渗透到磷酸化区域。值得注意的是，高表达的磷酸酶CD45被排除在信号域外。我们的结果表明，在T细胞与APC接触位点生理性的TCR触发是细胞内激酶和磷酸酶之间平衡的局部改变的结果。因此，我们提供了实验证据来支持基于CD45被排除在TCR信号区域之外的当前T细胞激活模型[2][3][4]。
