Cloning and expression of mouse integrin beta p(beta 7): a functional role in Peyer's 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.
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Howard Hughes Medical Institute, Department of Pathology, Stanford University School of Medicine, CA 94305.
Crowe
D T
DT
Weissman
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IL
Holzmann
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D016023:Integrins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010581:Peyer's Patches / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D016201:Receptors, Lymphocyte Homing / Q000235:genetics*
D000911:Antibodies, Monoclonal; D016023:Integrins; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D004247:DNA