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Antibody Binding Specificity for Kappa (Vκ) Light Chain-containing Human (IgM) Antibodies: Polysialic Acid (PSA) Attached to NCAM as a Case Study
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Mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Its binding motif for alpha 4 beta 7 and role in experimental

S Fong1, S Jones, M E Renz

  • 1Department of Immunology, Genentech, Inc., San Francisco, CA 94080-4990, USA. fong.sherman@gene.com

Immunologic Research
|January 1, 1997
PubMed

Insights

The interaction between integrin alpha 4 beta 7 and MAdCAM-1 is crucial for lymphocyte recirculation in the gut. Specific amino acid residues (LDT) in MAdCAM-1 mediate this interaction, impacting cell adhesion and activation in colitis models.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Integrin alpha 4 beta 7 and MAdCAM-1 facilitate lymphocyte homing to the gastrointestinal tract.
  • These molecules are implicated in the pathogenesis of inflammatory conditions like colitis.

Purpose of the Study:

  • To elucidate the structural basis of the interaction between integrin alpha 4 beta 7 and MAdCAM-1.
  • To identify key residues in MAdCAM-1 responsible for its function with alpha 4 beta 7.

Main Methods:

  • Site-directed mutagenesis was employed to modify the MAdCAM-1 molecule.
  • The functional consequences of these mutations on alpha 4 beta 7 binding and cell activation were assessed.

Main Results:

  • The amino acid triplet LDT within MAdCAM-1 was identified as critical for adhesive function with alpha 4 beta 7.
  • This LDT motif is located in the loop between beta strands C and D of the Ig-superfamily-like domain.
  • Alterations in LDT affected both the adhesive and cell-activating properties of MAdCAM-1.

Conclusions:

  • The LDT motif in MAdCAM-1 is essential for mediating interactions with integrin alpha 4 beta 7.
  • Understanding this interaction provides insights into lymphocyte trafficking in the gut and inflammatory diseases.
  • Targeting the alpha 4 beta 7-MAdCAM-1 pathway, specifically the LDT interaction, could offer therapeutic strategies for colitis.

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