Role of ligands in the activation of LFA-1

Lymphocyte function-associated-antigen-1 (LFA-1) is able to bind selectively to its ligands intercellular adhesion molecules 1 and 3 (ICAM-1 and ICAM-3), suggesting that LFA-1 can exist in distinct ligand-specific binding states. In the case of ICAM-1, apart from ligand itself and the recently cloned molecule cytohesin-1, the natural physiological regulators of LFA-l-mediated binding to ICAM-1 are unknown. We have investigated the role of ligands (ICAM-1 and ICAM-3) in LFA-1 activation by using ICAM-blocking monoclonal antibodies and a fixation protocol for ''freezing'' LFA-1 on the surface of cells after prior exposure to ICAM-1 and ICAM-3. These studies not only confirm that LFA-1 exists in distinct ICAM-specific activation states, but also demonstrate that ICAM-1 plays a role in the activation of LFA-1 binding to ICAM-3.