Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering.
Integrins are heterodimeric cell surface proteins that mediate both cell-cell and cell-extracellular matrix interactions. We and others recently identified cDNAs encoding a novel integrin beta subunit, beta 7, in lymphocytes. We have now detected beta 7 mRNA in mouse TK-1 T lymphoma cells, which are known to express the putative Peyer's patch homing receptor alpha 4 beta P. We used an anti-peptide antiserum and a novel mAb against the beta 7 subunit to show that TK-1 cells express beta 7 as the only subunit associated with alpha 4. We conclude that beta 7 and beta P are identical. We also show that activated peripheral blood T cells express alpha 4 beta 7. We studied the function of alpha 4 beta 7/alpha 4 beta P in TK-1 cells, which do not express very late antigen (VLA)-4 (alpha 4 beta 1). Cells adhered to intact fibronectin and to a fibronectin fragment containing the CS-1 region, but not to a fragment containing the RGD sequence. Adhesion to fibronectin was inhibited by antibodies to alpha 4, suggesting that alpha 4 beta 7 is a fibronectin receptor. We confirmed that alpha 4 beta 7 binds to the CS-1 region of fibronectin using affinity chromatography. TK-1 cell adhesion to the vascular cell adhesion molecule VCAM-1 was also inhibited by antibodies to alpha 4, implying that alpha 4 beta 7 also plays a role in the adherence of lymphocytes to endothelial cells. TK-1 cell binding to fibronectin and VCAM-1 is markedly increased by brief PMA stimulation. We also found that mAbs against alpha 4 and beta 7 induce homotypic clustering of TK-1 cells. Taken together these results suggest that alpha 4 beta 7/alpha 4 beta P recognizes some or all of the same widely distributed ligands recognized by VLA-4 (alpha 4 beta 1) and that the role of alpha 4 beta 7/alpha 4 beta P may not be restricted to lymphocyte homing.
Department of Medicine, University of California, San Francisco 94143.
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Rüegg
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Postigo
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Sikorski
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Butcher
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Pytela
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Erle
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002460:Cell Line; D005353:Fibronectins; D015870:Gene Expression; D006801:Humans; D007106:Immune Sera; D016023:Integrins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D005353:Fibronectins; D007106:Immune Sera; D016023:Integrins; D010455:Peptides; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1