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用抗淋巴细胞功能相关抗原-1(LFA-1)和抗LYT-2、3单克隆抗体阻断细胞毒性T淋巴细胞(CTL)介导的杀伤作用。I. 木瓜蛋白酶处理靶细胞后阻断作用增强的易感性。

Blocking of CTL-mediated killing by monoclonal antibodies to LFA-1 and LYT-2,3. I. Increased susceptibility to blocking after papain treatment of target cells.

作者信息

Gromkowski S H, Heagy W, Sanchez-Madrid F, Springer T A, Martz E

出版信息

J Immunol. 1983 Jun;130(6):2546-51.

PMID:6406593
Abstract

It is now established that monoclonal antibodies (MAb) against LFA-1 and Lyt-2,3 antigens on cytolytic T lymphocytes (CTL) block killing function in the absence of C. It has been suggested that the blocking is inversely related to CTL-target affinity. In this report, we studied the effect of papain pretreatment of target cells, because papain is known to remove H-2 and to render target cells more resistant to allospecific CTL. CTL-target conjugate formation was weaker with papain-treated target cells (based on reduced post-dispersion lysis in dextran-containing medium). The concentration of MAb required to produce 40 to 60% inhibition of 51Cr release (2-hr assay) was reduced four to 29-fold for alpha LFA-1 and 64 to 114-fold for alpha Lyt-2,3. Papain, however, did not induce blocking by MAb to other CTL antigens such as Thy-1, H-2, and T200. Flow cytometric analysis confirmed that papain selectively removed more than 95% of H-2. In kinetic studies of removal and recovery, H-2 density and conjugate formation correlated well with each other. Sensitivity to blocking was not as well correlated, raising the possibility that an unidentified papain-sensitive target cell molecule other than H-2 plays an important role in CTL-target interaction.

摘要

现已证实,针对细胞毒性T淋巴细胞(CTL)上LFA-1和Lyt-2,3抗原的单克隆抗体(MAb)在无补体(C)的情况下可阻断杀伤功能。有人提出这种阻断作用与CTL-靶细胞亲和力呈负相关。在本报告中,我们研究了木瓜蛋白酶预处理靶细胞的效果,因为已知木瓜蛋白酶可去除H-2并使靶细胞对同种特异性CTL更具抗性。经木瓜蛋白酶处理的靶细胞形成的CTL-靶细胞结合较弱(基于含葡聚糖培养基中分散后裂解减少)。产生51Cr释放40%至60%抑制(2小时测定)所需的MAb浓度,对于αLFA-1降低了4至29倍,对于αLyt-2,3降低了64至114倍。然而,木瓜蛋白酶并未诱导MAb对其他CTL抗原(如Thy-1、H-2和T200)产生阻断作用。流式细胞术分析证实,木瓜蛋白酶选择性去除了超过95%的H-2。在去除和恢复的动力学研究中,H-2密度与结合形成彼此密切相关。对阻断的敏感性相关性较差,这增加了除H-2之外的未鉴定的木瓜蛋白酶敏感靶细胞分子在CTL-靶细胞相互作用中起重要作用的可能性。

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