Streptavidin blocks immune reactions mediated by fibronectin-VLA-5 recognition through an Arg-Gly-Asp mimicking site.
Streptavidin is a biotin-binding analogue of egg-white avidin which is secreted by the bacterium Streptomyces avidinii. We have recently reported that streptavidin contains an Arg-Tyr-Asp-Ser (RYDS) sequence which exhibits structural homology to the Arg-Gly-Asp-Ser (RGDS) cell adhesion domain of fibronectin and other matrix-associated glycoproteins. Competition studies with RGD peptides indicated that streptavidin binds to cells via this site and that the binding is independent of biotin recognition. Since the RGD-containing peptide has been shown to play a key role in integrin-mediated cell adhesion, we assumed that streptavidin may utilize the RYDS site to bind to immune cells and thereby abrogate their adhesion-dependent functions. We now report that streptavidin modulates several matrix-dependent interactions of immune cells. In this context, immobilized streptavidin was found to support activated human CD4+ T cell adhesion in an RGD-specific, alpha 5 beta 1-dependent manner. In addition, soluble streptavidin (the commercially available or biotin-blocked forms) inhibited T cell adhesion to fibronectin and interfered with its co-stimulatory effect on tumor necrosis factor-alpha secretion by co-cultures of CD4+ T cells and macrophages. These results suggest that streptavidin is a novel example of a bacterial protein which utilizes RGD mimicry to interfere with integrin-mediated immune responses.
Alon
R
R
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Hershkoviz
R
R
Bayer
E A
EA
Wilchek
M
M
Lider
O
O
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry*; D002448:Cell Adhesion / Q000187:drug effects; D005353:Fibronectins / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D017469:Receptors, Fibronectin / Q000037:antagonists & inhibitors*; D017474:Receptors, Laminin / Q000378:metabolism; D019809:Streptavidin
D001426:Bacterial Proteins; D005353:Fibronectins; D007797:Laminin; D017469:Receptors, Fibronectin; D017474:Receptors, Laminin; D019809:Streptavidin