Bonnard M, Maroun C R, Julius M
Department of Immunology, University of Toronto, Wellesley Hospital Research Institute, Ontario, Canada.
Cell Immunol. 1997 Jan 10;175(1):1-11. doi: 10.1006/cimm.1996.1044.
CD45 is a family of transmembrane protein tyrosine phosphatases that are essential to T lymphocytes' responses to antigen-receptor stimulation. It is involved in the regulation of Src-family protein tyrosine kinases, Lck and Fyn. The object of this study was to determine how CD45 molecules are directed to such substrates at the antigen-receptor complex upon stimulation of resting T cells. We demonstrate that CD45 is physically associated with CD4 in resting, primary lymph node T cells. Further, CD4-dependent, antigen-mediated activation of primary CD4+ T cells results in disruption of CD4-CD45 complexes, suggesting a role for these complexes in the activation process. Moreover, CD45 coprecipitates with CD4 molecules which are associated with Lck, as well as with those which are not associated with Lck. Consistent with these observations and the role of CD45 in the regulation of Lck function, effects on CD4-associated membrane Lck are demonstrable. Since antigen presentation by MHC class II results in the coaggregation of CD4 with the antigen-receptor complex, the association described in this study provides a physical basis through which CD45 could be included.
CD45是一个跨膜蛋白酪氨酸磷酸酶家族，对T淋巴细胞对抗原受体刺激的反应至关重要。它参与Src家族蛋白酪氨酸激酶Lck和Fyn的调节。本研究的目的是确定在静息T细胞受到刺激时，CD45分子如何在抗原受体复合物处被导向此类底物。我们证明，在静息的初级淋巴结T细胞中，CD45与CD4存在物理关联。此外，依赖CD4的、抗原介导的初级CD4+ T细胞激活导致CD4 - CD45复合物的破坏，提示这些复合物在激活过程中发挥作用。而且，CD45与和Lck相关的CD4分子以及与Lck不相关的CD4分子共沉淀。与这些观察结果以及CD45在Lck功能调节中的作用一致，对与CD4相关的膜Lck有明显影响。由于II类主要组织相容性复合体（MHC）提呈抗原会导致CD4与抗原受体复合物的共聚集，本研究中描述的这种关联提供了一个可纳入CD45的物理基础。
