Leo O, Foo M, Henkart P A, Perez P, Shinohara N, Segal D M, Bluestone J A
Transplantation Biology Section, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1987 Dec 1;139(11):3556-63.
Accessory molecules present on the cell surface of cytolytic T lymphocytes (CTL) play an important role in their activation. Antigen-specific recognition by CTL is inhibited by antibodies against Lyt-2, L3T4, or LFA-1 molecules. Presently it is not known whether these molecules function by binding a ligand such as class I or class II on the target cell or by delivering a signal that down-regulates T cell activation. In the present study we utilized anti-T cell antibodies including anti-T3 and anti-T cell receptor (alpha/beta) as well as an anti-Ly-6.2C monoclonal antibody to activate CTL clones to kill irrelevant targets or secrete BLT esterase. The redirected lysis assay system utilizes the fact that heteroconjugates between anti-T3, and anti-T cell receptor, or anti-Ly-6.2C and anti-trinitrophenyl can trigger CTL lysis of trinitrophenyl-coupled targets that did not express antigen. In this system anti-Lyt-2 antibodies as well as anti-LFA-1 antibodies inhibited triggering via T cell receptor-related molecules but not via the anti-Ly-6.2C heteroconjugate. In addition, the anti-Lyt-2 was shown to inhibit conjugate formation in the heteroaggregate assay system suggesting that the anti-Lyt-2 antibodies acted early in inhibiting CTL activity. Similar results were observed in a system in which the CTL clones were triggered to secrete a BLT-esterase-like activity in the absence of target cells. Anti-T3 coated on plastic was shown to activate BLT-esterase secretion. This secretion was inhibited by anti-Lyt-2 and anti-LFA-1. Thus, it would appear that both the Lyt-2 molecule and the LFA-1 molecule act as signal-transducing elements involved in CTL activation. In particular, the Lyt-2 molecule appears to preferentially function in receptor-mediated T cell activation.
细胞毒性T淋巴细胞（CTL）细胞表面存在的辅助分子在其激活过程中发挥着重要作用。针对Lyt-2、L3T4或LFA-1分子的抗体可抑制CTL的抗原特异性识别。目前尚不清楚这些分子是通过与靶细胞上的I类或II类配体结合发挥作用，还是通过传递下调T细胞激活的信号发挥作用。在本研究中，我们利用抗T细胞抗体，包括抗T3和抗T细胞受体（α/β）以及抗Ly-6.2C单克隆抗体来激活CTL克隆，以杀伤无关靶细胞或分泌BLT酯酶。重定向裂解分析系统利用了这样一个事实，即抗T3与抗T细胞受体之间或抗Ly-6.2C与抗三硝基苯基之间的异源缀合物可触发CTL对未表达抗原的三硝基苯基偶联靶细胞的裂解。在该系统中，抗Lyt-2抗体以及抗LFA-1抗体抑制通过T细胞受体相关分子的触发，但不抑制通过抗Ly-6.2C异源缀合物的触发。此外，在异源聚集体分析系统中，抗Lyt-2被证明可抑制缀合物形成，这表明抗Lyt-2抗体在早期就发挥抑制CTL活性的作用。在一个系统中观察到了类似的结果，在该系统中，CTL克隆在无靶细胞的情况下被触发分泌类似BLT酯酶的活性。涂覆在塑料上的抗T3被证明可激活BLT酯酶分泌。这种分泌受到抗Lyt-2和抗LFA-1的抑制。因此，Lyt-2分子和LFA-1分子似乎都作为参与CTL激活的信号转导元件发挥作用。特别是，Lyt-2分子似乎在受体介导的T细胞激活中优先发挥作用。
