Expression of αv and β3 integrin chains on murine lymphocytes

Abstract

The vitronectin receptor is a member of the integrin family of adhesion protein receptors and binds a broad spectrum of ligands, including fibronectin and fibrinogen in addition to vitronectin. We have generated four mAbs that recognize the murine ␣v␤3 vitronectin receptor. Biochemical and expression analyses showed that two of the mAbs are specific for the ␣v chain, and two are specific for the ␤3 chain. The mAbs are effective blocking reagents and inhibited cell adhesion to vitronectin, fibrinogen, and fibronectin. Staining analysis revealed expression of ␣v and ␤3 on certain populations of murine thymocytes, splenocytes, and bone marrow cells. The expression of ␣v and ␤3 appeared to be modulated at specific stages of thymocyte development, suggesting a possible function for the ␣v␤3 vitronectin receptor in T cell development.Integrins comprise a large family of heterodimeric cell surface proteins composed of ␣ and ␤ chains that mediate cell-cell interactions and interactions between cells and the extracellular matrix (ECM) (1-3). Integrins are expressed on all cells and are involved in a number of fundamental cell processes including adhesion, migration, activation, and differentiation. The expression and functions of integrins have been particularly well-studied with respect to lymphocytes, which require a variety of cell-cell and cell-ECM interactions to perform their complex programs of immune surveillance and antigen response (4, 5). The functions of integrins depend on binding to specific adhesion proteins, such as fibronectin, often through recognition of the tripeptide, arginine-glycine-aspartic acid (RGD), binding motif (6).The human ␣v␤3 vitronectin receptor was originally identified as a heterodimeric molecule with vitronectin binding activity (7), and later shown to be related to other members of the integrin family (8). Subsequent studies demonstrated that this receptor has a broad binding specificity and can mediate binding to fibronectin, fibrinogen, von Willebrand factor, and thrombospondin in addition to vitronectin (9-12). More recently, a mAb specific for the murine ␣v␤3 vitronectin receptor (␣v␤3) was isolated (13,14), and used to identify ␣v␤3 as a costimulatory molecule required for spontaneous activation of ␥␦ T cell hybridomas (15).In the process of identifying cell surface molecules involved in the constitutive interleukin 2 (IL-2) secretion of murine V␥1, V␦6 T cell hybridomas, we generated a series of monoclonal antibodies (mAbs) that recognize murine ␣v␤3. Here, we present the characterization of four of these mAbs, including the determination of their chain specificities and staining analysis of several lymphoid populations. Contrary to previous reports (13, 16), we observed detectable levels of ␣v and ␤3 expression on certain populations of thymocytes and splenocytes in addition to bone marrow cells. Interestingly, we observed differential expression of the ␣v and ␤3 chains on discrete populations of thymocytes, suggesting a possible role for this receptor in T cell develo...

A novel regulatory role of gp49B on dendritic cells in T‐cell priming

“…3A, a substantial proportion of, or most of the OT-II CD4 1 T cells expressed the integrin a v or b 3 chain, respectively. On the other hand, while the majority of OT-I CD8 1 T cells showed expression of the integrin b 3 chain, their a v chain expression was low, as essentially described previously [38], suggesting that this gp49B ligand is more abundant in OT-II CD4 1 T cells than OT-I CD8 1 T cells.…”

“…3A, a substantial proportion of, or most of the OT-II CD4 1 T cells expressed the integrin a v or b 3 chain, respectively. On the other hand, while the majority of OT-I CD8 1 T cells showed expression of the integrin b 3 chain, their a v chain expression was low, as essentially described previously [38], suggesting that this gp49B ligand is more abundant in OT-II CD4 1 T cells than OT-I CD8 1 T cells.Next, OVA-primed and irradiated BMDC from gp49B À/À and B6 mice were co-cultured with OT-II CD4 1 T cells and OT-I CD8 1 T cells at the indicated T-cell: DC ratios, and the proliferative response of T cells was determined as [ 3 H]thymidine uptake on day 3. gp49B À/À BMDC showed augmented antigen presentation to both OT-II CD4 1 T cells and OT-I CD8 1 T cells compared with B6 BMDC (Fig. 3B).…”

“…On the other hand, our present study demonstrated that, despite the comparable maturation statuses of or cytokine production by gp49B À/À and B6 BMDC, gp49B À/À BMDC showed augmented MHC class I and class II-restricted antigen presentation compared with B6 BMDC in vitro. Our transwell study confirmed that the direct DC-T interaction, at least in the initial phase, was necessary for effective antigen presentation by gp49B À/À DC.A ligand for gp49B, integrin a v b 3 [30], is expressed on T cells [38], and several reports have indicated that integrin a v b 3 -mediated signaling can activate T cells [44,45]. Moreover, integrin a v b 3 expression is upregulated on activated T cells [32], suggesting that integrin a v b 3 positively regulates immune responses at the interface between DC and T cells.…”

“…A ligand for gp49B, integrin a v b 3 [30], is expressed on T cells [38], and several reports have indicated that integrin a v b 3 -mediated signaling can activate T cells [44,45]. Moreover, integrin a v b 3 expression is upregulated on activated T cells [32], suggesting that integrin a v b 3 positively regulates immune responses at the interface between DC and T cells.…”

Regulatory T cell-like responses in deer mice persistently infected with Sin Nombre virus

“…(43), an entry determinant for hantaviruses (44). This might result in the disabling of virus-specific T cells during the acute phase of the adaptive immune response.…”