Breitmeyer J B, Daley J F, Levine H B, Schlossman S F
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA.
J Immunol. 1987 Nov 1;139(9):2899-905.
Most mature human T lymphocytes express both the multichain T3 (CD3)/Ti T cell receptor for antigen (TCR), and the biochemically distinct 55-kDa T11 (CD2) glycoprotein. Stimulating the T11 molecule causes profound T cell proliferation and functional activation in vitro, but the relationship of T11-mediated activation to antigenic stimulation of T lymphocytes in vivo remains unknown. We now present evidence that T11 function is directly linked to TCR components in T3/Ti+ T11+ human T cells. First, we found that stimulating peripheral blood T cells with the mitogenic combination of anti-T11(2) cells with the mitogenic combination of anti-T11(2) plus anti-T11(3) monoclonal antibodies caused the phosphorylation of TCR T3 chains. The predominance of T3-gamma-phosphorylation that occurred in anti-T11(2) plus anti-T11(3)-treated T cells is similar to the pattern previously observed in antigen-stimulated T cell clones. Second, T11 function depended upon concurrent cell-surface expression of the TCR. Thus, when peripheral blood T cells were deprived of cell surface T3/Ti by anti-T3 modulation, anti-T11(2) plus anti-T11(3)-induced mitogenesis and transmembrane signal generation in the form of calcium mobilization were inhibited. The mechanism of TCR-T11 interdependence was investigated in a series of TCR-deficient variants of a T cell lymphoblastoid cell line. T3/Ti negative variants expressed cell surface T11, but anti-T11(2) plus anti-T11(3) failed to cause detectable calcium mobilization. The TCR-deficient variants also failed to express T11(3) activation epitopes after incubation with anti-T11(2) antibodies, suggesting that T11(3) expression is an essential and TCR-dependent intermediate in the T11 activation mechanism in these cells. Taken together, our results suggest that T11 function depends upon cell-surface expression of TCR in many T3/Ti+ T11+ T lymphocytes, and T11-mediated activation is intimately interconnected with TCR activation mechanisms. A model in which stimulating signals delivered via T11 may be a part of antigenic activation of T lymphocytes is presented.
大多数成熟的人类T淋巴细胞同时表达多链T3（CD3）/Ti抗原T细胞受体（TCR）和生化性质不同的55-kDa T11（CD2）糖蛋白。在体外，刺激T11分子会引起T细胞的大量增殖和功能激活，但T11介导的激活与体内T淋巴细胞的抗原刺激之间的关系仍不清楚。我们现在提供证据表明，在T3/Ti⁺T11⁺人类T细胞中，T11功能与TCR组分直接相关。首先，我们发现用抗T11（2）加上抗T11（3）单克隆抗体的促有丝分裂组合刺激外周血T细胞，会导致TCR T3链的磷酸化。在抗T11（2）加上抗T11（3）处理的T细胞中发生的T3-γ磷酸化占优势，这与先前在抗原刺激的T细胞克隆中观察到的模式相似。其次，T11功能依赖于TCR在细胞表面的同时表达。因此，当通过抗T3调节使外周血T细胞缺乏细胞表面T3/Ti时，抗T11（2）加上抗T11（3）诱导的有丝分裂和以钙动员形式的跨膜信号产生受到抑制。在一个T细胞淋巴母细胞系的一系列TCR缺陷变体中研究了TCR-T11相互依赖的机制。T3/Ti阴性变体表达细胞表面T11，但抗T11（2）加上抗T11（3）未能引起可检测到的钙动员。TCR缺陷变体在与抗T11（2）抗体孵育后也未能表达T11（3）激活表位，这表明T1（3）表达是这些细胞中T11激活机制中一个必不可少且依赖于TCR的中间环节。综上所述，我们的结果表明，在许多T3/Ti⁺T11⁺T淋巴细胞中，T11功能依赖于TCR在细胞表面的表达，并且T11介导的激活与TCR激活机制密切相关。提出了一个模型，其中通过T11传递的刺激信号可能是T淋巴细胞抗原激活的一部分。
