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, alpha E beta 7) 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 o f intra-epithelial lymphocytes to intestinal enterocytes via an interaction with HML-1. Herein we report that both dimeric and monomeric forms of reco mbinant mouse E-cadherin-human immunoglobulin Fc chimera self-associate and support attachment of E-cadherin(+) mouse colon epithelial cells. Both for ms also support the adhesion of mouse MTC-1 T cells via M290, thereby estab lishing M290 as the functional mouse homologue of HML-1 and revealing that E-cadherin hemophilic and heterophilic binding sites are distinct. Adhesion of MTC-1 cells to E-cadherin-Fe was inhibited by arginine-glycine-aspartat e (RGD) peptides and vice versa cells bound to immobilized RGD polymer in a n M290-dependent fashion, where adhesion was inhibitable with soluble E-cad herin-Fc. Hence, E-cadherin and RGD integrin ligands antagonize cell bindin g by one another, either by inducing integrin cross-talk or by binding to s hared or overlapping sites within M290. Binding of E-cadherin-Fc by HML-1 c ostimulated the CD3-induced proliferation of purified CD4(+) T cells, sugge sting that E-cadherin expressed on dendritic cells may play a T cell costim ulatory role in addition to facilitating dendritic cell-keratinocyte adhesi on.