The cytosolic protein talin induces an intermediate affinity integrin αLβ2

Abstract

The integrin αLβ2 mediates leukocyte adhesion and migration that are required for a functional immune system. It is known that inside-out signaling triggers αLβ2 conformational changes, which affect its ligand-binding affinity. At least three αLβ2 affinity states (low, intermediate, and high) were described. The cytosolic protein talin connects α Lβ2 to the actin filament. The talin head domain is also known to activate αLβ2 ligand binding. However, it remains to be determined whether talin promotes an intermediate or high affinity αLβ2. In this study using transfectants and T cells, we showed that talin induced an intermediate affinity αLβ2 that adhered constitutively to its ligand intercellular adhesion molecule (ICAM)-1 but not ICAM-3. Adhesion to ICAM-3 was induced when an additional exogenous activating agent was included. Similar profiles were observed with soluble ICAMs. In addition, the intermediate affinity αLβ2 induced by talin allowed adhesion and migration of T cells on immobilized ICAMs. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.