Distinct but overlapping epitopes are involved in α4β7-mediated adhesion to vascular cell adhesion molecule-1, mucosal addressin-1, fibronectin, and lymphocyte aggregation

D. P. Andrew, C. Berlin, S. Honda, T. Yoshino, A. Hamann, B. Holzmann, P. J. Kilshaw, E. C. Butcher

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

The mouse CD8+ T cell lymphoma TK1 expresses high levels of α4β7 integrin, which it can use to interact with multiple ligands including mucosal addressin-1 (MAdCAM-1), VCAM-1, and fibronectin. In addition, α4β7- can support TK1 cell aggregation. Here we have produced and characterized a panel of mAbs against α4β7 to define antigenic and functional epitopes associated with its distinct functions. One mAb, DATK32, is unique in recognizing an epitope specific to the α4β7 heterodimer. Furthermore, DATK32 induces TK1 cell aggregation yet inhibits TK1 cell adhesion to MAdCAM-1, VCAM-1, and fibronectin. Considered as a whole, the panel of anti-α4β7 mAbs studied define unique patterns of inhibition for α4β7 binding to each of its defined molecular ligands. We conclude that α4β7 interactions with MAdCAM-1, VCAM-1, and fibronectin can be modulated by Ab binding to distinct epitopes and thus probably involve functionally separable, although physically overlapping binding sites on this multifunctional integrin. These findings are consistent with the general observation that integrins use distinct, potentially differentially regulated interaction sites for adhesion to multiple ligands. Extension of these concepts to α4β7 has important considerations for understanding the roles of this integrin in lymphocyte homing to mucosal sites and in cell-cell interactions during the immune response.

Original languageEnglish
Pages (from-to)3847-3861
Number of pages15
JournalJournal of Immunology
Volume153
Issue number9
Publication statusPublished - Jan 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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