Synergistic T cell activation via the physiological ligands for CD2 and the T cell receptor.
Synergistic T cell activation via the physiological ligands for CD2 and the T cell receptor.
复制标题
通过生理配体的CD2和T细胞受体的协同T细胞激活。
DOI：
10.1084/jem.168.3.1145
复制
发表时间：
1988-09-01
影响因子：
15.3
通讯作者：
BURAKOFF, SJ
中科院分区：
文献类型：
--
作者：
BIERER, BE;PETERSON, A;GORGA, JC;HERRMANN, SH;BURAKOFF, SJ
T 细胞可以被抗原特异性 T 细胞受体 (TCR)-CD3 复合物或细胞表面受体 CD2 激活。已发现 CD2 的天然配体是淋巴细胞功能相关抗原 3 (LFA-3)，一种广泛分布的细胞表面糖蛋白。为了研究这两条途径的相互作用，我们在小鼠 T 细胞杂交瘤中表达了编码人 CD2 分子的 cDNA，该杂交瘤响应 HLA-DR 抗原而产生 IL-2。 CD2 分子的表达显着增强了 LFA-3+ 抗原刺激细胞对 IL-2 的产生反应，并且这种刺激可被抗 CD2 和抗 LFA-3 mAb 抑制。为了进一步明确 LFA-3 在抗原依赖性 T 细胞激活中的作用，我们研究了纯化的 CD2 配体和 TCR 刺激杂交瘤的能力。含有纯化的HLA-DR抗原的脂质体和含有纯化的LFA-3的脂质体都不能刺激亲本或CD2+杂交瘤。然而，含有纯化的LFA-3和HLA-DR（分别是CD2和TCR的生理配体）的脂质体刺激CD2+而不是亲本杂交瘤产生IL-2，这表明TCR-CD3复合物和CD2途径之间的互补相互作用可能调节淋巴细胞活化。为了确定 CD2/LFA-3 相互作用是否参与细胞间粘附并提供激活信号，我们构建了 CD2 的细胞质缺失突变体 CD2 delta B，其中 CD2 的 COOH 末端 100 个氨基酸已被丝氨酸取代。对表达CD2 delta B分子的杂交瘤进行了检查。 CD2胞质结构域的缺失并没有改变LFA-3的结合，但消除了CD2增加杂交瘤对含有HLA-DR和LFA-3的脂质体的反应的能力，表明LFA-3与CD2的单独粘附不足以激活，并且胞质结构域是通过CD2分子刺激LFA-3所必需的。 T 细胞可以通过纯化的 LFA-3 与 CD2 结合以及 TCR 与其配体相互作用来激活，并且这些信号似乎对 T 细胞具有协同作用。这些结果表明 CD2/LFA-3 相互作用不仅在细胞间粘附中发挥作用，而且为 T 细胞激活提供刺激信号。
T cells may be activated either by the antigen-specific T cell receptor (TCR)-CD3 complex or the cell surface receptor CD2. A natural ligand for CD2 has been found to be lymphocyte function-associated antigen 3 (LFA-3), a widely distributed cell surface glycoprotein. To investigate the interaction of these two pathways, we have expressed the cDNA encoding the human CD2 molecule in a murine T cell hybridoma that produces IL-2 in response to HLA-DR antigens. Expression of the CD2 molecule markedly enhances IL-2 production in response to LFA-3+ antigen-bearing stimulator cells, and this stimulation is inhibited by anti-CD2 and anti-LFA-3 mAb. To further define the role of LFA-3 in antigen-dependent T cell activation, we have studied the ability of the purified ligands of CD2 and the TCR to stimulate the hybridoma. Neither liposomes containing purified HLA-DR antigens nor liposomes containing purified LFA-3 were able to stimulate the parent or the CD2+ hybridoma. However, liposomes containing both purified LFA-3 and HLA-DR, the physiological ligands for CD2 and the TCR, respectively, stimulate IL-2 production by the CD2+ but not the parent hybridoma, suggesting that complementary interactions between the TCR-CD3 complex and the CD2 pathway may regulate lymphocyte activation. To determine whether the CD2/LFA-3 interaction participates in cell-cell adhesion and provides an activation signal, we have constructed a cytoplasmic deletion mutant of CD2, CD2 delta B, in which the COOH-terminal 100 amino acids of CD2 have been replaced with a serine. Hybridomas expressing the CD2 delta B molecule were examined. Deletion of the cytoplasmic domain of CD2 did not alter binding of LFA-3 but eliminated the ability of CD2 to increase the response of the hybridoma to liposomes containing both HLA- DR and LFA-3, demonstrating that adhesion of LFA-3 to CD2 alone was insufficient for activation, and that the cytoplasmic domain was required for LFA-3 stimulation through the CD2 molecule. T cells may be activated by purified LFA-3 binding to CD2 and the TCR interacting with its ligand, and these signals appear to be synergistic for the T cell. These results suggest that the CD2/LFA-3 interaction not only plays a role in cell-cell adhesion but provides a stimulatory signal for T cell activation.
登录
查看更多内容
DOI：
10.1073/pnas.85.4.1194
发表时间：
1988-02-01
影响因子：
11.1
作者：
BIERER, BE;PETERSON, A;BURAKOFF, SJ
通讯作者：
BURAKOFF, SJ
影响因子：
4.3
作者：
GORGA, JC;KNUDSEN, PJ;BURAKOFF, SJ
通讯作者：
BURAKOFF, SJ
影响因子：
64.8
作者：
HUNIG, T;TIEFENTHALER, G;MEUER, SC
通讯作者：
MEUER, SC
影响因子：
64.8
作者：
SELVARAJ, P;PLUNKETT, ML;SPRINGER, TA
通讯作者：
SPRINGER, TA
影响因子：
5.4
作者：
MORETTA, A;OLIVE, D;MORETTA, L
通讯作者：
MORETTA, L