Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, England
Correspondence: Dr. N. Hogg, Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, Lincoln’s Inn Fields, London WC2A 3PX, England. E-mail: hogg{at}icrf.icnet.uk
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 comes
about as a result of increased integrin clustering. Affinity regulation
of integrins also plays a role, but the conformational changes giving
rise to increased affinity appear to be secondary to clustering.
Conformationally altered LFA-1 can be created artificially by deletion
of the I domain, which is the key domain involved in ligand binding for
many but not all integrins. Although I domain-deleted LFA-1
(
I-LFA-1) cannot bind ligand, it is able to signal constitutively
into the cell. One measure of this signaling activity is the ability of
I-LFA-1 to activate ß1 integrins on the same T lymphocyte.
Leukocytes use LFA-1 to migrate across the endothelium. Active ß1
integrins may be required subsequently to bind the matrix proteins
encountered by leukocytes as they continue their voyage into the tissue
interior.
Key Words: integrin structure • integrin activation • I domain
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