Structure-Function Analysis of the Integrin β7 Subunit: Identification of Domains Involved in Adhesion to MAdCAM-1

Mark Tidswell, Russell Pachynski, Steve W. Wu, Shi Qiang Qiu, Elizabeth Dunham, Nancy Cochran, Michael J. Briskin, Peter J. Kilshaw, Andrew I. Lazarovits, David P. Andrew, Eugene C. Butcher, Ted A. Yednock, David J. Erle

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85 Scopus citations

Abstract

β7 integrins serve special roles in mucosal immunity. α4β7-mediated adhesion to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) directs lymphocyte homing to the gut, and αEβ7 mediates binding of lymphocytes to E-cadherin on epithelial cells Since α4β7 mediates adhesion to MAdCAM-1 but α4β1 does not, we used β71 chimeras to directly assess the importance of specific regions of β7 in MAdCAM-1 binding. We found a region of β7 (residues 46-386) that accounts for specificity of α4β7 binding to MAdCAM-1. We also used human/mouse and human/rat chimeric β7 subunits to map epitopes recognized by fifteen anti-β7 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 β7 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 αL and αM. Three new Abs that recognize β7 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 β7 integrin-mediated adhesion.

Original languageEnglish
Pages (from-to)1497-1505
Number of pages9
JournalJournal of Immunology
Volume159
Issue number3
StatePublished - Aug 1 1997

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