Mouse M290 is the functional homologue of the human mucosal lymphocyte integrin HML-1: antagonism between the integrin ligands E-cadherin and RGD tripeptide.
Human mucosal lymphocyte antigen-1 (HML-1, alphaEbeta7) and E-cadherin, two members of unrelated cell adhesion superfamilies, have evolved to play cooperative roles in gut mucosal immunity. Human E-cadherin is self-ligand mediating intercellular adhesion of epithelial cells, as well as adhesion of intra-epithelial lymphocytes to intestinal enterocytes via an interaction with HML-1. Herein we report that both dimeric and monomeric forms of recombinant mouse E-cadherin-human immunoglobulin Fc chimera self-associate and support attachment of E-cadherin+ mouse colon epithelial cells. Both forms also support the adhesion of mouse MTC-1 T cells via M290, thereby establishing M290 as the functional mouse homologue of HML-1 and revealing that E-cadherin homophilic and heterophilic binding sites are distinct. Adhesion of MTC-1 cells to E-cadherin-Fc was inhibited by arginine-glycine-aspartate (RGD) peptides and vice versa cells bound to immobilized RGD polymer in an M290-dependent fashion, where adhesion was inhibitable with soluble E-cadherin-Fc. Hence, E-cadherin and RGD integrin ligands antagonize cell binding by one another, either by inducing integrin cross-talk or by binding to shared or overlapping sites within M290. Binding of E-cadherin-Fc by HML-1 costimulated the CD3-induced proliferation of purified CD4+ T cells, suggesting that E-cadherin expressed on dendritic cells may play a T cell costimulatory role in addition to facilitating dendritic cell-keratinocyte adhesion.
Berg
R W
RW
Department of Molecular Medicine, School of Medicine and Health Science, University of Auckland, Auckland, New Zealand.
Yang
Y
Y
Lehnert
K
K
Krissansen
G W
GW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003110:Colonic Neoplasms / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D019281:Dimerization; D006801:Humans; D018928:Immunity, Mucosal; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured
D015820:Cadherins; D017931:DNA Primers; D016023:Integrins; D008024:Ligands; D009842:Oligopeptides; C070709:integrin alphaEbeta7; C047981:arginyl-glycyl-aspartic acid