Monoclonal antibodies targeting murine LFA-1 induce LFA-1/ICAM-1-independent homotypic lymphocyte aggregation.
We have identified three anti-murine LFA-1 alpha monoclonal antibodies (M17/4.2, G-48, and FD441.8) which are capable of inducing homotypic aggregation of murine T cell lines (3A9 EL-4 cells). The LFA-1-induced aggregation is temperature-dependent, necessitates metabolic energy, and requires an intact cytoskeleton, but is independent of transcription and protein synthesis. The aggregation is inhibited in Ca2+ and Mg2+ free media and is also blocked with EDTA and EGTA. The aggregation does not involve protein kinase A or C or changes in intracellular calcium. The LFA-1 alpha-induced homotypic aggregation is inhibited with LFA-1 beta antibodies, but not with antibodies targeting ICAM-1, VCAM-1, VLA-4, or CD2. 3A9 cells do not express the LFA-1 ligand ICAM-1, whereas EL-4 cells express moderate amounts of ICAM-1. Thus, targeting LFA-1 alpha with mAb results in homotypic aggregation of T cell lines which is independent of ICAM-1/LFA-1 interactions, but may involve other LFA-1 ligands such as ICAM-2 or ICAM-3. Alternatively, LFA-1 may function as a signaling molecule, triggering other yet to be defined adhesion molecules to interact.
Division of Nephrology, University of Alabama, Birmingham 35294.
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Wuthrich
D000818:Animals; D000911:Antibodies, Monoclonal; D001386:Azides / Q000494:pharmacology; D002118:Calcium; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002449:Cell Aggregation / Q000187:drug effects*; D002460:Cell Line; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008274:Magnesium; D051379:Mice; D019810:Sodium Azide; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001386:Azides; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D019810:Sodium Azide; D008274:Magnesium; D002118:Calcium