Regulated expression and binding of three VLA (β1) integrin receptors on T cells

Abstract

Regulated adhesion of T cells to extracellular matrix (ECM) proteins is likely to be essential in T cell migration. Constitutive binding of various other cell types to ECM components is mediated by members of the VLA (very late antigen) subfamily of integrins. We describe here the regulated binding of resting CD4+ human T cells to ECM through three VLA integrins: VLA-4 and VLA-5 binding to fibronectin (FN), and a novel pathway of VLA-6 binding to laminin (LN). Binding to ECM is regulated in two ways. First, unlike other VLA-mediated interactions, VLA binding activity of the T cells is rapidly and dramatically augmented with cell activation without change in level of expression of the VLA molecules. Second, binding is regulated with T-cell differentiation; memory T cells express three- to four-fold more VLA-4, VLA-5, and VLA-6 than do naive cells, and bind more efficiently through them to FN and LN.

β1 Integrin-dependent binding of Jurkat cells to fibronectin is regulated by a serine-threonine phosphatase

“…In addition to the amount of expression of cell surface adhesion molecules, the functional state of integrins can be regulated, leading to changes in the affinity for counterligand binding without affecting the level of cell surface expression [11]. Changes in T cell integrin activity can be induced in vitro by a variety of stimulating agents, such as phorbol esters, calcium ionophore, and cross-linking of T cell receptors like CD2, CD3, CD7, and CD28 [3,[12][13][14]. Furthermore, the activation state of integrins can be altered by antibodies against ␤ 1 integrins, like 8A2, that bind to the receptor and induce a more active form [15] or by alterations of the extracellular cation milieu, both of which appear to affect the conformation of the integrin binding site [16,17].…”

“…Among those of the ␤ 1 family, VLA-3 (␣ 3 ␤ 1 ), VLA-4 (␣ 4 ␤ 1 ), VLA-5 (␣ 5 ␤ 1 ), and VLA-6 (␣ 6 ␤ 1 ) can be constitutively expressed on peripheral blood T lymphocytes [2]. These mediate binding to the extracellular matrix components collagen (through VLA-3), laminin (through VLA-6), and Fn (through both VLA-4 and VLA-5) [2,3]. VLA-4 binds to the alternatively spliced connecting segment III (CS1) domain of Fn [4][5][6][7], whereas VLA-5 binds to Fn via the RGD sequence, distinct from the CS1 domain to which VLA-4 binds [8].…”

From the ECM to the Cytoskeleton and Back: How Integrins Orchestrate T Cell Action

“…Although T lymphocytes exhibit high rates of migration (Serrador et al, 1999) (Shaw et al, 1986 Shimizu et al, 1990b;. This suggests that a critical function of co-receptor signaling during T cell activation is to enhance integrin-mediated adhesive forces that are necessary for effective stimulation of T cells (Zell et al, 1998a).…”

Expression and function of beta1 integrins on human eosinophils

“…Several activation stimuli have been shown to upregulate integrin function. Treatment of T cells with PMA or the Ca+2 ionophore A23187 has been shown to upregulate integrin-mediated T-cell adhesion, indicating that both protein kinase C and Ca+2 are involved in the intracellular signaling events (Shimizu et al 1990), whereas treatment of Jurkat cells with the serine-threonine phosphatase inhibitor okadaic acid depresses fibronectin adhesion through β1 integrins (Seminario et al 1997). Furthermore, cell-surface receptors, called integrin regulators, can induce an inside-out signal.…”