ICAM-3 INTERACTS WITH LFA-1 AND REGULATES THE LFA-1/ICAM-1 CELL-ADHESION PATHWAY
ICAM-3 INTERACTS WITH LFA-1 AND REGULATES THE LFA-1/ICAM-1 CELL-ADHESION PATHWAY
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DOI：
10.1083/jcb.123.4.1007
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发表时间：
1993-11-01
影响因子：
7.8
通讯作者：
SANCHEZMADRID, F
中科院分区：
文献类型：
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作者：
CAMPANERO, MR;DELPOZO, MA;SANCHEZMADRID, F
淋巴细胞功能相关抗原-1（LFA-1）与其配体的相互作用介导了免疫应答过程中重要的多个细胞粘附过程。我们已经获得了三个抗ICAM-3的单克隆抗体，识别两个不同的表位（A和B）的细胞间粘附分子3（ICAM-3）的顺序免疫沉淀和交叉竞争的单克隆抗体结合实验证明。免疫亲和纯化的ICAM-3包被的表面能够支持T淋巴母细胞在用佛波醇酯和交联的CD 3刺激细胞时的附着，以及通过LFA-1分子与活化的抗LFA 1 NKI-L16 mAb的mAb接合。用针对LFA-1 α（CD 11 a）或LFA-β（CD 18）整联蛋白链的mAb预处理细胞，可完全抑制T细胞与纯化ICAM-3的粘附。抗ICAM-3单克隆抗体特异性表位A，但不特异性表位B，能够触发T淋巴母细胞同型聚集。ICAM-3介导的细胞聚集依赖于LFA-1/ICAM-1途径，如用特异于LFA-1和ICAM-1分子的mAb的阻断实验所证明的。此外，ICAM-3诱导的细胞聚集的免疫荧光研究表明，LFA-1和ICAM-1主要位于细胞间的边界。ICAM-3位于细胞尾足类，其在小聚集体中似乎与细胞-细胞接触有关，而在大聚集体中似乎被排除在细胞-细胞接触区域之外。T细胞粘附于嵌合ICAM-1-Fc分子的实验显示，促聚集性抗ICAM-3 HP 2/19 mAb能够增加T淋巴母细胞与ICAM-1的粘附，表明该mAb诱导的T细胞聚集可以通过增加LFA-1对ICAM-1的亲合力来介导。此外，HP 2/19 mAb与抗CD 3 mAb对T淋巴细胞增殖具有共刺激作用，表明T细胞活化的增强可能参与ICAM-3介导的粘附现象。总之，我们的研究结果表明，ICAM-3对细胞间粘附的LFA-1/ICAM-1途径具有调节作用。
The interaction of lymphocyte function-associated antigen-1 (LFA-1) with its ligands mediates multiple cell adhesion processes of capital importance during immune responses. We have obtained three anti-ICAM-3 mAbs which recognize two different epitopes (A and B) on the intercellular adhesion molecule-3 (ICAM-3) as demonstrated by sequential immunoprecipitation and cross-competitive mAb-binding experiments. Immunoaffinity purified ICAM-3-coated surfaces were able to support T lymphoblast attachment upon cell stimulation with both phorbol esters and cross-linked CD3, as well as by mAb engagement of the LFA-1 molecule with the activating anti-LFA1 NKI-L16 mAb. T cell adhesion to purified ICAM-3 was completely inhibited by cell pretreatment with mAbs to the LFA-1alpha (CD11a) or the LFA-beta (CD18) integrin chains. Anti-ICAM-3 mAbs specific for epitope A, but not those specific for epitope B, were able to trigger T lymphoblast homotypic aggregation. ICAM-3-mediated cell aggregation was dependent on the LFA-1/ICAM-1 pathway as demonstrated by blocking experiments with mAbs specific for the LFA-1 and ICAM-1 molecules. Furthermore, immunofluorescence studies on ICAM-3-induced cell aggregates revealed that both LFA-1 and ICAM-1 were mainly located at intercellular boundaries. ICAM-3 was located at cellular uropods, which in small aggregates appeared to be implicated in cell-cell contacts, whereas in large aggregates it appeared to be excluded from cell-cell contact areas. Experiments of T cell adhesion to a chimeric ICAM-1-Fc molecule revealed that the proaggregatory anti-ICAM-3 HP2/19 mAb was able to increase T lymphoblast attachment to ICAM-1, suggesting that T cell aggregation induced by this mAb could be mediated by increasing the avidity of LFA-1 for ICAM-1. Moreover, the HP2/19 mAb was costimulatory with anti-CD3 mAb for T lymphocyte proliferation, indicating that enhancement of T cell activation could be involved in ICAM-3-mediated adhesive phenomena. Altogether, our results indicate that ICAM-3 has a regulatory role on the LFA-1/ICAM-1 pathway of intercellular adhesion.