Shape and shift changes related to the function of leukocyte integrins LFA-1 and Mac-1

Integrin activity on leukocytes is controlled tightly, ensuring that ligand binding occurs only when leukocytes are in contact with their targets. For an integrinlike LFA-1, this ligand-binding activity conies about as a resu lt of increased integrin clustering. Affinity regulation of integrins also plays a role, but the conformational changes giving rise to increased affin ity appear to be secondary to clustering. Conformationally altered LFA-1 ca n be created artificially by deletion of the I domain, which is the hey dom ain involved hi ligand binding for many but not all integrins, Although I d omain-deleted LFA-1 (DeltaI-LFA-1) cannot bind Ligand, it is able to signal constitutively into the cell. One measure of this signaling activity is th e ability of DeltaI-LFA-I to activate beta1 integrins on the same T lymphoc yte. Leukocytes use LFA-1 to migrate across the endothelium. Active beta1 i ntegrins may be required subsequently to bind the matrix proteins encounter ed by leukocytes as they continue their voyage into die tissue interior.