MODULATION OF SURFACE T11 MOLECULES INDUCED BY MONOCLONAL-ANTIBODIES - ANALYSIS OF THE FUNCTIONAL-RELATIONSHIP BETWEEN ANTIGEN-DEPENDENT AND ANTIGEN-INDEPENDENT PATHWAYS OF HUMAN T-CELL ACTIVATION
MODULATION OF SURFACE T11 MOLECULES INDUCED BY MONOCLONAL-ANTIBODIES - ANALYSIS OF THE FUNCTIONAL-RELATIONSHIP BETWEEN ANTIGEN-DEPENDENT AND ANTIGEN-INDEPENDENT PATHWAYS OF HUMAN T-CELL ACTIVATION
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DOI：
10.1002/eji.1830161118
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发表时间：
1986-11-01
影响因子：
5.4
通讯作者：
MORETTA, L
中科院分区：
文献类型：
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作者：
MORETTA, A;OLIVE, D;MORETTA, L
先前的数据表明，分别针对“T112”和“T113”opitopes的抗t11单克隆抗体（mAb）组合可以激活T淋巴细胞。与针对T3-T细胞受体（Ti）复合物或T44分子的抗体诱导的T细胞活化不同，抗T11单抗诱导的细胞活化不伴随着T11抗原的表面调节。在目前的研究中，我们发现抗T11单抗的适当刺激组合能够在多种T细胞中诱导T11抗原调节，包括多克隆外周血群、正常以及白血病（JA3） T细胞克隆。第一个抗T11单抗组合既能激活细胞又能调节T11抗原，其中一个单抗靶向T112表位，另一个单抗识别属于T111组的表位。第二种组合是由针对T111组的两个不同决定因子的两个单抗给予的。诱导T11抗原调节的能力可以更精确地分析由T11分子启动的T细胞激活途径及其与其他已知T细胞激活途径的物理和功能关系。T11抗原调节后的T细胞对随后的抗T11单抗刺激没有反应。不应期为48 ~ 72 h，对抗T11单抗的应答性恢复与细胞表面T11分子的重新表达一致。T11抗原的调节不影响T3、Ti或T44分子的表面表达，此外，“被调节”的细胞保持了对针对T3、Ti或T44分子的单抗的应答能力。相反，抗体诱导的T3-Ti受体复合物的调节消除了T11和t44依赖性T细胞的激活。最后，抗体诱导的T44抗原的调节不会抑制T细胞激活的T11-或t3 - ti依赖途径。这些数据表明，T11分子引发的T细胞活化途径的下调不仅可以通过抗原受体复合物的调节来诱导，还可以通过对T11分子的适当单抗来诱导，并且可能通过与T11分子结合的天然配体来诱导。
Previous data indicated that T lymphocyte activation can be achieved by using a combination of anti-T11 monoclonal antibodies (mAb) directed to the "T112" and the "T113" opitopes, respectively. Unlike the T cell activation induced by antibodies directed to the T3-T cell receptor (Ti) complex or to T44 molecules, the anti-T11 mAb-induced cell activation was not accompanied by surface modulation of the T11 antigen. In the present study we show that appropriate stimulatory combinations of anti-T11 mAb are able to induce T11 antigen modulation in a variety of T cells including polyclonal peripheral blood populations, normal as well as leukemic (JA3) T cell clones. The first anti-T11 mAb combination leading to both cell activation and T11 antigen modulation was given by a mAb directed to the T112 epitope and by another mAb recognizing an epitope belonging to the T111 group. The second combination was given by two mAb directed against two different determinants of the T111 group. The ability to induce T11 antigen modulation allowed a more precise analysis of the pathway of T cell activation initiated by T11 molecules and its physical and functional relationship with the other known pathways of T cell activation. T cells following T11 antigen modulation failed to respond to subsequent stimulation with anti-T11 mAb. The refractory period lasted for 48-72 h and the restoration of the responsiveness to anti-T11 mAb coincided with the re-expression of T11 molecules at the cell surface. Modulation of T11 antigen did not affect the surface expression of T3, Ti or T44 molecules, in addition, "modulated" cells maintained their ability to respond to mAb directed against T3, Ti or T44 molecules. On the contrary, antibody-induced modulation of the T3-Ti receptor complex abrogated both T11- and T44-dependent T cell activation. Finally, antibody-induced modulation of T44 antigen did not inhibit either the T11- or the T3-Ti-dependent pathway of T cell activation. These data indicate that down-regulation of the pathway of T cell activation initiated by T11 molecules can be induced not only by modulation of the antigen receptor complex but also by appropriate mAb to T11 molecules and, presumably, by the natural ligand binding to T11 molecules.