Streptavidin blocks immune reactions mediated by fibronectin-VLA-5 recognition through an Arg-Gly-Asp mimicking site

Eur J Immunol. 1993 Apr;23(4):893-8. doi: 10.1002/eji.1830230419.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / pharmacology*
  • CD4-Positive T-Lymphocytes / chemistry*
  • Cell Adhesion / drug effects
  • Fibronectins / antagonists & inhibitors*
  • Humans
  • In Vitro Techniques
  • Laminin / metabolism
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Receptors, Fibronectin / antagonists & inhibitors*
  • Receptors, Laminin / metabolism
  • Streptavidin


  • Bacterial Proteins
  • Fibronectins
  • Laminin
  • Receptors, Fibronectin
  • Receptors, Laminin
  • Streptavidin