A novel monoclonal antibody recognizing a cation-dependent epitope within the regulatory loop of human β1 integrin (CD29)

Jean Pierre Lévesque, Yoshikazu Takada, Wilma Puzon-McLaughlin, Paul J. Simmons

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Cell adhesion receptors of the integrin superfamily can be expressed in different affinity states towards their ligands. It has been previously demonstrated that β1 integrins α4β1 and α5β1 are expressed in a nonligand binding form by human hemopoietic progenitor cells but can be activated into a ligand binding form by a variety of stimuli including intracellular stimuli generated by cytokine receptors and extracellular stimuli generated by function-activating anti-β1 integrin monoclonal antibodies (MAbs). In both instances, the activation of β1 integrins is believed to be the result of conformational changes propagating along the β1 integrin chain which in turn increase accessibility to the ligand. A cluster of either function-activating or function-inhibiting anti-β1 integrin MAbs have been shown to bind within a 12 amino acid long regulatory loop between residues 207 and 218 of the humanβ1 integrin chain. We describe in this report the first MAb (96.9H9) specific for this regulatory loop whose binding is cation-dependent and requires either Ca2+ or Mn2+ but not Mg2+. In addition, the activation of α4β1 and α5β1 integrins by 96.9H9 is a two-step process with distinct cation requirements. Whereas Ca2+ is sufficient to promote binding of the antibody to the β1 integrin chain, Mg2+ is necessary for activating function following 96.9H9 binding. Our data therefore suggest that the regulatory epitope of the human β1 integrin chain is flexible with multiple conformations according to the cationic environment.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalHybridoma and Hybridomics
Volume21
Issue number4
Publication statusPublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Immunology

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