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Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1.

Beta 7 integrins serve special roles in mucosal immunity. Alpha 4 beta 7-mediated adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs lymphocyte homing to the gut, and alpha E beta 7 mediates binding of lymphocytes to E-cadherin on epithelial cells. Since alpha 4 beta 7 mediates adhesion to MAdCAM-1 but alpha 4 beta 1 does not, we used beta 7/beta 1 chimeras to directly assess the importance of specific regions of beta 7 in MAdCAM-1 binding. We found a region of beta 7 (residues 46-386) that accounts for specificity of alpha 4 beta 7 binding to MAdCAM-1. We also used human/mouse and human/rat chimeric beta 7 subunits to map epitopes recognized by fifteen anti-beta 7 mAbs. Six of seven Abs that block adhesion to MAdCAM-1 and E-cadherin (Fib 21, 22, 27, 30, 504; Act-1) mapped to amino acid residues 176-250. Residues 176-250 lie within the region of beta 7 that specifies MAdCAM-1 binding and also within a region that has a predicted structure homologous to the metal ion-dependent adhesion site (MIDAS) domains of the integrin subunits alpha L and alpha M. Three new Abs that recognize beta 7 in the presence of Mn2+, but not Ca2+, and promote adhesion to MAdCAM-1, mapped to amino acids 46-149. One blocking and five other Abs mapped to other regions (amino acids 387-725). We conclude that a MIDAS-like domain serves a critical role in beta 7 integrin-mediated adhesion.

Pubmed ID: 9233649


  • Tidswell M
  • Pachynski R
  • Wu SW
  • Qiu SQ
  • Dunham E
  • Cochran N
  • Briskin MJ
  • Kilshaw PJ
  • Lazarovits AI
  • Andrew DP
  • Butcher EC
  • Yednock TA
  • Erle DJ


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

August 1, 1997

Associated Grants

  • Agency: NIAID NIH HHS, Id: AI37832
  • Agency: NHLBI NIH HHS, Id: K08HL03230
  • Agency: NHLBI NIH HHS, Id: R01HL52004

Mesh Terms

  • Animals
  • Antibodies, Monoclonal
  • Cations
  • Cell Adhesion Molecules
  • Epitope Mapping
  • Humans
  • Immunoglobulins
  • Integrin beta Chains
  • Integrins
  • Leukemia, Erythroblastic, Acute
  • Ligands
  • Mice
  • Molecular Sequence Data
  • Mucoproteins
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Receptors, Lymphocyte Homing
  • Recombinant Fusion Proteins
  • Serine
  • Structure-Activity Relationship
  • Transfection
  • Tumor Cells, Cultured