Activation of the alpha 4 beta 1 integrin through the beta 1 subunit induces recognition of the RGDS sequence in fibronectin.
Lymphocyte attachment to fibronectin is mainly mediated by the interaction of alpha 5 beta 1 and alpha 4 beta 1 integrins with the RGD and CS-1/Hep II sites, respectively. We have recently shown that the anti-beta 1 mAb TS2/16 can convert the partly active alpha 4 beta 1 present on certain hemopoietic cells that recognizes CS-1 but not Hep II, to a high avidity form that binds both ligands. In this report we have studied whether mAb TS2/16 also affects alpha 4 beta 1 ligand specificity. Incubation of the B cell lines Ramos and Daudi (which lack alpha 5 beta 1) with mAb TS2/16 induced specific attachment to an 80-kD fragment which lacks CS-1 and Hep II and contains the RGD sequence. mAbs anti-alpha 4 and the synthetic peptides CS-1 and IDAPS inhibited adhesion to the 80-kD fragment thus implying alpha 4 beta 1 as the receptor for this fragment. Interestingly, the synthetic peptide GRGDSPC and a 15-kD peptic fibronectin fragment containing the RGD sequence also inhibited B cell adhesion to the 80-kD fragment. Because we have previously shown that RGD peptides do not affect the constitutive function of alpha 4 beta 1, we tested whether TS2/16-activated alpha 4 beta 1 acquired the capacity to recognize RGD. Indeed RGD peptides inhibited TS2/16-treated B cell adhesion to a 38-kD fragment containing CS-1 and Hep II but did not affect binding of untreated cells to this fragment. An anti-fibronectin mAb reactive with an epitope on or near the RGD sequence also efficiently inhibited cell adhesion to the 80-kD fragment, indicating that the RGD sequence is a novel adhesive ligand for activated alpha 4 beta 1. These results emphasize the role of alpha 4 beta 1 as a receptor with different ligand specificities according to the activation state, a fact that may be important for lymphocyte migration, localization, and function.
Sánchez-Aparicio
P
P
Departamento de Inmunología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Dominguez-Jiménez
C
C
Garcia-Pardo
A
A
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D017469:Receptors, Fibronectin / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D005353:Fibronectins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D008024:Ligands; D010446:Peptide Fragments; D017469:Receptors, Fibronectin; D039441:Integrin alpha4; D013755:Tetradecanoylphorbol Acetate