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The leukocyte integrin alpha D beta 2 binds VCAM-1: evidence for a binding interface between I domain and VCAM-1.

The trafficking of leukocytes through tissues is supported by an interaction between the beta 2 (CD18) integrins CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1) and their ligand ICAM-1. The most recently identified and fourth member of the beta 2 integrins, alpha D beta 2, selectively binds ICAM-3 and does not appear to bind ICAM-1. We have reported recently that alpha D beta 2 can support eosinophil adhesion to VCAM-1. Here we demonstrate that expression of alpha D beta 2 in a lymphoid cell that does not express alpha 4 integrins confers efficient binding to VCAM-1. In addition, a soluble form of alpha D beta 2 binds VCAM-1 with greater efficiency relative to ICAM-3. The I domain of alpha D contains a binding site for VCAM-1 since recombinant alpha D I domain binds specifically to VCAM-1. In addition, alpha D mAb that block cellular binding to VCAM-1 bind the alpha D I domain. Using VCAM-1 mutants we have determined that the binding site on VCAM-1 for alpha D beta 2 overlaps with that of alpha 4++ integrins. Substitution of VCAM-1 aspartate at position 40, D40, within the conserved integrin binding site, diminishes binding to alpha D beta 2 and abrogates binding to the alpha D I domain. The corresponding integrin binding site residue in ICAM-3 is also essential to alpha D beta 2 binding. Finally, we demonstrate that alpha D beta 2 can support lymphoid cell adhesion to VCAM-1 under flow conditions at levels equivalent to those mediated by alpha 4 beta 1. These results indicate that VCAM-1 can bind to an I domain and that the binding of alpha D beta 2 to VCAM-1 may contribute to the trafficking of a subpopulation of leukocytes that express alpha D beta 2.

Pubmed ID: 10438935


  • Van der Vieren M
  • Crowe DT
  • Hoekstra D
  • Vazeux R
  • Hoffman PA
  • Grayson MH
  • Bochner BS
  • Gallatin WM
  • Staunton DE


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

August 15, 1999

Associated Grants


Mesh Terms

  • Animals
  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, CD11
  • Binding Sites
  • Binding Sites, Antibody
  • Cell Adhesion
  • Cell Movement
  • Humans
  • Integrin alpha Chains
  • Integrin alpha4
  • Integrins
  • Jurkat Cells
  • Leukocytes
  • Mice
  • Mice, Inbred BALB C
  • Peptide Fragments
  • Protein Binding
  • Receptors, Cytoadhesin
  • Recombinant Proteins
  • Rheology
  • Vascular Cell Adhesion Molecule-1