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Vol. 11, Issue 2, 677-690, February 2000
2
Integrin Lymphocyte Function-associated Antigen-1
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund,
London WC2A 3PX, United Kingdom
A subset of integrin 
subunits contain an I domain,
which is important for ligand binding. We have deleted the I domain
from the 
2 integrin lymphocyte function-asssociated
antigen-1 (LFA-1) and expressed the resulting non-I domain-containing
integrin (
I-LFA-1) in an LFA-1-deficient T cell line.
I-LFA-1 showed no recognition of LFA-1 ligands, confirming the
essential role of the I domain in ligand binding. Except for I domain
monoclonal antibodies (mAbs), I-LFA-1 was recognized by a panel of
anti-LFA-1 mAbs similarly to wild-type LFA-1. However,
I-LFA-1 had enhanced expression of seven mAb epitopes that are
associated with 2 integrin activation, suggesting that it
exhibited an "active" conformation. In keeping with this
characteristic, I-LFA-1 induced constitutive activation of 41
and 51, suggesting intracellular signaling to these integrins. This "cross-talk" was not due to an effect on
1 integrin affinity. However, the enhanced activity was
susceptible to inhibition by cytochalasin D, indicating a role for the
cytoskeleton, and also correlated with clustering of 1
integrins. Thus, removal of the I domain from LFA-1 created an
integrin with the hallmarks of a constitutively active receptor
mediating signals into the cell. These findings suggest a key role for
the I domain in controlling integrin activity.
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