gp49B1-αvβ3 interaction inhibits antigen-induced mast cell activation

Abstract

We have identified the integrin αvβ3 as a ligand for mouse gp49B1, thus identifying a new class of ligand for a member of the family of inhibitory immunoreceptors that bear C2-type immunoglobulin-like domains. The specific interaction was shown by both cell-protein and cell-cell binding assays. In addition, we found that the interaction of αvβ3 with gp49B1 on bone marrow–derived mouse mast cells inhibited antigen-induced immunoglobulin E–mediated cell activation. Because neither gp49B1 nor αvβ3 exhibit substantive allelic variation, their newly appreciated interaction may reflect an innate pathway for down-regulating the activity of mast cells.

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Figure 1: Aggregation of T cells with P815.gp49B1 transfectants.
Figure 2: Binding of BY155.16 cells and human K562. αvβ3 transfectants to plate-bound gp49B1-Fc.
Figure 3: Binding of mouse P815.gp49B1 transfectants to plate-bound human αvβ3 and inhibition of vitronectin binding to αvβ3 by gp49B1-Fc.
Figure 4: Cell-cell interactions between BMMCs expressing gp49B1 and BY155.16 cells expressing αvβ3.
Figure 5: Inhibition of IgE-dependent BMMC activation by solid-phase αvβ3.

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Acknowledgements

We thank M. Brenner and C. Parker for advice and X.-Y. Wu, L. Rodriguez, B. Sampson, A. Bass, E.Wasser and M. Diaz Jara for technical assistance. Supported by NIH grants AI-01414, AI-07306, AI-22531, AI-31599, AI-41144, AR-45025, AR-47243 and HL-36110 and by grants from the Hyde and Watson Foundation, Arthritis Foundation and Osteogenesis Imperfecta Foundation.

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Correspondence to Mariana C. Castells.

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Castells, M., Klickstein, L., Hassani, K. et al. gp49B1-αvβ3 interaction inhibits antigen-induced mast cell activation. Nat Immunol 2, 436–442 (2001). https://doi.org/10.1038/87749

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