Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha.
Lymphocyte homing is controlled by organ-specific interactions of lymphocytes and high endothelial venules (HEV). Adhesion of lymphocytes to Peyer's patch HEV, but not to peripheral node HEV, is inhibited by an antibody recognizing the murine lymphocyte antigen LPAM-1. Lymphoma cell variants were selected on the FACS for differences in LPAM-1 expression: the binding capacity of these variants to Peyer's patch HEV directly correlates with the level of LPAM-1 expression. The anti-LPAM-1 antibody recognizes the alpha subunit of an Mr 160,000/130,000 cell surface alpha beta heterodimer. The association of LPAM-1 alpha and beta chains requires the presence of Ca2+ ions. Proteins of Mr 84,000 and Mr 62,000 present in LPAM-1 immunoprecipitates appear to be products of the proteolytic processing of alpha chains. The structure of LPAM-1 is virtually identical to that of the human integrin receptor VLA-4. The cross-reactivity of a monospecific rabbit antiserum demonstrated the similarity between the human VLA-4 alpha chain and the alpha subunit of LPAM-1.
Holzmann
B
B
Department of Pathology, Stanford University School of Medicine, California 94305.
McIntyre
B W
BW
Weissman
I L
IL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000502:physiology*; D000954:Antigens, Surface / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D003429:Cross Reactions; D004730:Endothelium, Vascular / Q000502:physiology; D000939:Epitopes; D016023:Integrins; D008214:Lymphocytes / Q000502:physiology*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D010449:Peptide Mapping; D010581:Peyer's Patches / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D000939:Epitopes; D016023:Integrins; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen