Induction of T-Cell Signaling by Immobilized Integrin Ligands

The integrin supergene family of adhesion molecules are cell surface αβ heterodimers (reviewed in ref. 1 ). Although most integrins are involved in the binding of cells to extracellular matrix (ECM) components, many T-cell integrins can also bind to cell surface ligands. CD4⁺ T helper (Th) cells can express several integrins, of which the best studied are the leukocyte function-associated antigen-1 (LFA-1), α_L β₂ (CD11a/CD18), and the very late activation antigen-4 (VLA-4), α₄ β₁ (CD49d/CD29). The highest affinity ligand for LFA-1 is the intercellular adhesion molecule-1 (ICAM-1) (CD54), which is a member of the immunoglobulin (Ig) supergene family. Other ligands for LFA-1 are the Ig supergene family members ICAM-2 (CD102) and ICAM-3 (CD50). VLA-4, the second functionally important integrin expressed on Th cells, can bind to both the ECM protein fibronectin and the cell surface expressed Ig supergene family member vascular adhesion molecule-1 (VCAM-1) (CD106).