LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 (LFA-1) - A SURFACE-ANTIGEN DISTINCT FROM LYT-2,3 THAT PARTICIPATES IN LYMPHOCYTE-T-MEDIATED KILLING
LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1 (LFA-1) - A SURFACE-ANTIGEN DISTINCT FROM LYT-2,3 THAT PARTICIPATES IN LYMPHOCYTE-T-MEDIATED KILLING
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DOI：
10.1073/pnas.78.7.4535
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发表时间：
1981-01-01
期刊：
影响因子：
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通讯作者：
SPRINGER, TA
中科院分区：
文献类型：
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作者：
DAVIGNON, D;MARTZ, E;SPRINGER, TA
用单克隆抗体（MAb）研究了溶细胞性T淋巴细胞（CTL）表面分子与CTL功能的关系。产生针对小鼠CTL的大鼠MAb。12个MA B与T细胞相比优先结合B细胞，其中3个识别以前未描述的表面多肽。测试这些MAb和更广泛反应性的先前获得的MAb在不存在补体的情况下阻断CTL介导的杀伤的能力。为了确保任何观察到的阻断是由于MAb与效应细胞而不是靶细胞的结合，使用异种小鼠CTL抗大鼠BN淋巴瘤靶细胞系统（MAb和靶细胞均为大鼠来源）。在24株单克隆抗体中，有21株对CTL活性影响很小或没有影响，包括对H-2、Thy-1、Lyt-1、Ly-5、Ly-6、Lgp-100和至少6种其它抗原的单克隆抗体。用针对Lyt-2，3的2种MAb证实杀伤的抑制。另一种单克隆抗体M7/14对CTL功能产生了深刻和一致的阻断。M7/14 MAb通过与小鼠CTL结合阻断杀伤，但不与用于CTL试验的大鼠淋巴瘤靶细胞结合。由M7/14定义的抗原，称为淋巴细胞功能相关抗原，LFA-1，可能参与CTL介导的杀伤机制或与CTL介导的杀伤机制密切相关。LFA-1含有分子量为180，000和95，000的2条多肽链，与其它已描述的淋巴细胞糖蛋白不同。因此，LFA-1代表了以前未描述的淋巴细胞表面抗原和用于阻断CTL介导的杀伤的分子位点。
Monoclonal antibodies (MAb) were used to probe the relationship of cytolytic T lymphocyte (CTL) surface molecules to CTL function. Rat MAb to mouse CTL were generated. Twelve MAb gave preferential binding to T cells as compared to B cells, and 3 of these recognized previously undescribed surface polypeptides. These MAb and more broadly reactive and previously obtained MAb were tested for their ability to block CTL-mediated killing in the absence of complement. To ensure that any observed blocking was due to binding of MAb to the effector cell rather than the target cell, a xenogeneic mouse CTL anti-rat BN lymphoma target cell system was utilized (MAb and target cells both of rat origin). Of 24 MAb tested here, 21 had little or no effect on CTL function, including those to H-2, Thy-1, Lyt-1, Ly 5 Ly 6, Lgp 100 and at least 6 other defined antigens. Inhibition of killing was confirmed with 2 MAb to Lyt-2,3. Another MAb, M7/14, gave profound and consistent blockade of CTL function. M7/14 MAb blocks killing by binding to the mouse CTL and does not bind to the rat lymphoma target cells used for the CTL assay. The antigen defined by M7/14, termed a lymphocyte function-associated antigen, LFA-1, probably participates in or is closely associated with the mechanism of CTL-mediated killing. LFA-1 contains 2 polypeptide chains with MW of 180,000 and 95,000 and is distinct from other described lymphocyte glycoproteins. LFA-1 thus represents both a previously undescribed lymphocyte surface antigen and molecular site for blockade of CTL-mediated killing.