Role of ligands in the activation of LFA‐1

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Abstract
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‐1‐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.