VLA-4-mediated signaling.

Abstract

The VLA (very late antigens) constitute the β1 subfamily of integrin adhesion receptors defined by at least nine α-chains that share a noncovalently linked common β-chain, termed β1 (CD29) (Hynes 1992; Schwartz 1993). The VLA mainly function as cell surface receptors mediating cell-to-cell and cell-to-extracellular matrix (ECM) adhesive interactions. They constitute a major class of adhesive receptors expressed by T cells. On resting CD4+ T cells, the VLA/CD29 antigens are preferentially expressed on the CD45RO+ CD45RA− helper/inducer (memory) subset (Morimoto et al. 1985). VLA molecules are thought to play a major role in the interaction between these helper cells and the surrounding ECM or aid their migration into tissues (Shimizu and Shaw 1991). Apart from a role in cell adhesion, recent studies have clearly shown the VLA receptors to transduce signals in a wide variety of cells, including T lymphocytes (Schwartz et al. 1991; Shattil and Brugge 1991; Sultan et al. 1991). For example, several laboratories, including ours, have shown that the binding of T cells with ECM through VLA- β1-integrins provides costimulatory signals for T cell proliferation (Matsuyama et al. 1989; Nojima et al. 1990; Yamada et al. 1991a, b; Ennis et al. 1993). VLA-β1-integrins are also reported to be involved in T or B cell differentiation through interaction with fibronectin (FN), expressed on stromal cells in thymus or bone marrow, respectively (Salomon et al. 1994; Williams et al. 1991).