CLONING AND EXPRESSION OF MOUSE INTEGRIN-BETA(P)(BETA(7)) - A FUNCTIONAL-ROLE IN PEYER PATCH-SPECIFIC LYMPHOCYTE HOMING

Lymphocytes express integrin receptors, termed lymphocyte Peyer's patch high endothelial venule (HEV) adhesion molecules (LPAMs), that mediate their organ-specific adhesion to specialized HEVs found in mucosal lymphoid organs (Peyer's patches). LPAM-1 consists of a murine integrin alpha-4 noncovalently associated with integrin beta(p). Here, we describe the cloning and expression of a mouse cDNA encoding beta(p), which is an 806-amino acid transmembrane glycoprotein. The genomic Southern blot analysis indicates that beta(p) is the murine homologue of human beta-7. The function of alpha-4-beta-7 as a Peyer's patch-specific adhesion molecule was tested directly by expression of the murine beta-7 cDNA in an alpha-4+-beta-7- B-cell line or coexpression of the alpha-4 and beta-7 cDNAs in an alpha-4--beta-7- T-cell line. The transfected cells exhibited a new Peyer's patch-specific adhesive phenotype that could be specifically blocked by monoclonal antibodies against alpha-4 and beta-7. Moreover, an anti-beta-7 monoclonal antibody specifically blocked binding of normal lymphocytes to Peyer's patch HEV but did not inhibit their binding to peripheral lymph node HEVs, indicating that beta-7 is a unique component of the Peyer's patch-specific homing receptor.