ICAM-3 interacts with LFA-1 and regulates the LFA-1/ICAM-1 cell adhesion pathway.

作者：Miguel R. Campanero, Miguel Á. del Pozo, Alicia G. Arroyo, Paloma Sánchez‐Mateos, Trinidad Hernández‐Caselles, Alister Gordon Craig, Rafael Pulido, Francisco Sánchez‐Madrid · 发表于：The Journal of Cell Biology · 年份：1993 · DOI：10.1083/jcb.123.4.1007 · 被引用次数：167 · 研究领域：Cell Adhesion Molecules Research、Immunotherapy and Immune Responses、T-cell and B-cell Immunology

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-LFA-1 NKI-L16 mAb. T cell adhesion to purified ICAM-3 was completely inhibited by cell pretreatment with mAbs to the LFA-1 alpha (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. Experimen...