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 β7/β1 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.
|Number of pages||9|
|Journal||Journal of Immunology|
|State||Published - Aug 1 1997|