A monoclonal antibody to VLA-4 alpha-chain (CDw49d) induces homotypic lymphocyte aggregation.
A monoclonal antibody to VLA-4 alpha-chain (CDw49d) induces homotypic lymphocyte aggregation.
复制标题
VLA-4 α 链 (CDw49d) 的单克隆抗体可诱导同型淋巴细胞聚集。
DOI：
10.4049/jimmunol.144.3.777
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发表时间：
1990
影响因子：
4.4
通讯作者：
B. McIntyre
中科院分区：
文献类型：
--
作者：
J. L. Bednarczyk;B. McIntyre
细胞黏附的复杂过程涉及多种受体与配体的相互作用，这在免疫功能的发展过程中极为重要。淋巴细胞被银或丝裂原激活，CTL和nk介导的细胞溶解，归巢到淋巴相关组织，以及淋巴细胞与细胞外基质蛋白的附着，都至少部分地由细胞表面粘附受体控制。在分析单克隆抗体阻断人类细胞毒性T淋巴细胞介导的杀伤能力时，注意到抑制性单克隆抗体引起CTL之间快速而剧烈的聚集。该抗体mAb L25也能诱导人T和B肿瘤细胞系聚集。mAb L25与整合素蛋白VLA-4的α 4亚基上的表位结合，诱导粘附事件，需要二价阳离子、能量、流体质膜和完整的细胞骨架。单抗L25诱导的ag非依赖性同型粘附不受单抗抑制，单抗对与Ag-1 （CD11a/CD18）、CD2、CD4和CD8相关的淋巴细胞功能，或对它们的配体ICAM-1、LFA-3、MHC I类或MHC II类的粘附也不受抑制。我们相信这些实验提示了VLA-4在一个新的白细胞粘附系统中的作用。
The complex processes of cellular adhesion involve a variety of receptor to ligand interactions that are extremely important during the development of immune function. Lymphocyte activation by Ag or mitogen, CTL- and NK-mediated cytolysis, homing to lymphoid-associated tissue, and the attachment of lymphocytes to extracellular matrix proteins are all governed, at least in part, by cell surface adhesion receptors. During the analysis of mAb for the ability to block human cytotoxic T lymphocyte-mediated killing an inhibitory mAb was noted that caused rapid and vigorous aggregation among the CTL. This antibody, mAb L25, also induced aggregation among human T and B tumor cell lines. mAb L25 binds to an epitope on the alpha 4 subunit of the integrin protein VLA-4 and induced an adhesion event requiring divalent cations, energy, a fluid plasma membrane, and an intact cytoskeleton. The Ag-independent homotypic adhesion induced by mAb L25 was not inhibited by mAb to the lymphocyte function associated Ag-1 (CD11a/CD18), CD2, CD4, and CD8, or to their ligands ICAM-1, LFA-3, MHC class I, or MHC class II. We believe that these experiments suggest a role for VLA-4 in a novel system of leukocyte adhesion.