Zhu De-Min, Dustin Michael L, Cairo Christopher W, Thatte Hemant S, Golan David E
Departments of Biological Chemistry and Molecular Pharmacology, Surgery, and Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
ACS Chem Biol. 2006 Nov 21;1(10):649-58. doi: 10.1021/cb6002515.
The CD2 receptor on T lymphocytes is essential for T cell adhesion and stimulation by antigen presenting cells (APCs). Blockade of CD2 function is immunosuppressive in both model systems and humans, indicating the importance of CD2 for the cellular immune response. Although the affinity of the molecular interaction between CD2 and its counter-receptor, CD58, is relatively low when measured in solution, this interaction mediates tight adhesion within the 2D cell-cell interface. To understand the mechanisms responsible for regulating the avidity of the CD2-CD58 interaction, we measured the number, affinity, and lateral mobility of CD2 molecules on resting and activated T cells. Cell activation caused a 1.5-fold increase in the number of CD2 sites on the cell surface, and the 2D affinity of CD2 for CD58 increased by 2.5-fold. The combination of T cell activation and CD2 ligation to CD58 decreased the laterally mobile fraction of the ligated CD2. Together, these changes would substantially enhance CD2 avidity and strengthen T cell-APC adhesion. The change in CD2 mobile fraction suggests that the cell uses cytoskeletal regulators to immobilize the receptor selectively at the site of contact with surfaces expressing CD58. Our observations are consistent with a model in which T cell activation initially induces increased CD2 2D affinity, cell surface receptor expression, and lateral mobility, allowing the CD2 molecules to diffuse to sites of contact with CD58-bearing APCs. Subsequently, T cell activation causes the CD58-bound CD2 to be recognized and immobilized at sites of cell-cell contact, thereby strengthening T cell-APC adhesion.
T淋巴细胞上的CD2受体对于T细胞与抗原呈递细胞（APC）的黏附及刺激至关重要。在模型系统和人类中，阻断CD2功能均具有免疫抑制作用，这表明CD2对细胞免疫反应具有重要意义。尽管在溶液中测量时，CD2与其配体受体CD58之间分子相互作用的亲和力相对较低，但这种相互作用介导了二维细胞-细胞界面内的紧密黏附。为了解调节CD2-CD58相互作用亲和力的机制，我们测量了静息和活化T细胞上CD2分子的数量、亲和力及侧向迁移率。细胞活化导致细胞表面CD2位点数量增加1.5倍，且CD2对CD58的二维亲和力增加了2.5倍。T细胞活化与CD2与CD58连接相结合，降低了连接的CD2的侧向迁移部分。这些变化共同作用将显著增强CD2亲和力并加强T细胞与APC的黏附。CD2迁移部分的变化表明，细胞利用细胞骨架调节因子将受体选择性地固定在与表达CD58的表面接触的部位。我们的观察结果与以下模型一致：T细胞活化最初诱导CD2二维亲和力、细胞表面受体表达及侧向迁移率增加，使CD2分子扩散至与携带CD58的APC接触的部位。随后，T细胞活化导致与CD58结合的CD2在细胞-细胞接触部位被识别并固定，从而加强T细胞与APC的黏附。
