The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1

P Altevogt, M Hubbe, M Ruppert, J Lohr, P von Hoegen, M Sammar, D P Andrew, L McEvoy, M J Humphries, E C Butcher

Research output: Contribution to journalArticlepeer-review


The heterodimeric alpha 4 integrins alpha 4 beta 7 lymphocyte Peyer's patch adhesion molecule ([LPAM]-1) and alpha 4 beta 1 (very late antigen-4) are cell surface adhesion molecules involved in lymphocyte trafficking and lymphocyte-cell and matrix interactions. Known cellular ligands include vascular cell adhesion molecule (VCAM)-1, which binds to alpha 4 beta 1 and alpha 4 beta 7, and the mucosal addressin cell adhesion molecule (MAdCAM)-1, which binds to alpha 4 beta 7. Here we show that the alpha 4 chain of these integrins can itself serve as a ligand. The alpha 4 chain, immunoaffinity purified and immobilized on glass slides, binds thymocytes and T lymphocytes. Binding exhibits divalent cation requirements and temperature sensitivity which are characteristic of integrin-mediated interactions, and is specifically inhibited by anti-alpha 4 integrin antibodies, which exert their effect at the cell surface. Cells expressing exclusively alpha 4 beta 7 (TK-1) or alpha 4 beta 1 (L1-2) both bound avidly, whereas alpha 4-negative cells did not. A soluble 34-kD alpha 4 chain fragment retained binding activity, and it inhibited lymphocyte adhesion to alpha 4 ligands. It has been shown that alpha 4 integrin binding to fibronectin involves an leucine-aspartic acid-valine (LDV) motif in the HepII/IIICS region of fibronectin (CS-1 peptide), and homologous sequences are important in binding to VCAM-1 and MAdCAM-1. Three conserved LDV motifs occur in the extracellular sequence of alpha 4. A synthetic LDV-containing alpha 4-derived oligopeptide supports alpha 4-integrin-dependent lymphocyte adhesion and blocks binding to the 34-kD alpha 4 chain fragment. Our results suggest that alpha 4 beta 7 and alpha 4 beta 1 integrins may be able to bind to the alpha 4 subunit on adjacent cells, providing a novel mechanism for alpha 4 integrin-mediated and activation-regulated lymphocyte interactions during immune responses.

Original languageEnglish
Pages (from-to)345-55
Number of pages11
JournalJournal of Experimental Medicine
Issue number2
Publication statusPublished - 1 Aug 1995


  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Cell Adhesion
  • Cell Adhesion Molecules
  • Integrins
  • Ligands
  • Lymphocytes
  • Mice
  • Molecular Sequence Data
  • Oligopeptides
  • Protein Binding
  • Receptors, Very Late Antigen
  • Sequence Alignment
  • Sequence Homology, Amino Acid


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