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.
Article|
August 01 1995
The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1.
P Altevogt,
P Altevogt
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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M Hubbe,
M Hubbe
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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M Ruppert,
M Ruppert
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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J Lohr,
J Lohr
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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P von Hoegen,
P von Hoegen
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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M Sammar,
M Sammar
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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D P Andrew,
D P Andrew
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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L McEvoy,
L McEvoy
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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M J Humphries,
M J Humphries
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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E C Butcher
E C Butcher
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
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P Altevogt
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
M Hubbe
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
M Ruppert
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
J Lohr
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
P von Hoegen
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
M Sammar
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
D P Andrew
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
L McEvoy
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
M J Humphries
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
E C Butcher
Tumor Immunology Programme, German Cancer Research Center, Heidelberg.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1995) 182 (2): 345–355.
Citation
P Altevogt, M Hubbe, M Ruppert, J Lohr, P von Hoegen, M Sammar, D P Andrew, L McEvoy, M J Humphries, E C Butcher; The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1.. J Exp Med 1 August 1995; 182 (2): 345–355. doi: https://doi.org/10.1084/jem.182.2.345
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