Control of beta1 integrin function. Localization of stimulatory epitopes.
The beta1 integrins can be expressed on the surface of cells in a latent form, which is activated by a variety of stimuli. As an approach to examining the transition to an active receptor, a panel of stimulatory antibodies to beta1 were produced and characterized. These antibodies induced adherence of the T-leukemic cell line Jurkat to collagen and fibronectin. Competitive antibody binding assays indicated the existence of at least three distinct epitope clusters A (B3B11, JB1B, 21C8), B (B44, 13B9), and C(N29) defined by the indicated antibodies. Two antibodies to the A site, JB1B and B3B11, were shown to localize to positions 671-703 and 657-670, respectively, of the beta1. This region is located in an area encompassing a predicted disulfide bond between linearly distant cysteines in beta1 (Cys415-Cys671). The homologous region of the beta3 integrin (490 690 and 602 690) has been shown to be one of the sites recognized by stimulatory antibodies to ligand-induced binding sites. The present results indicate the existence of multiple stimulatory regions and suggest considerable homology between the locations of beta1 and beta3 regulatory sites.
Wilkins
J A
JA
Rheumatic Disease Unit Research Laboratory, Department of Internal Medicine, University of Manitoba, Winnipeg MB R3A 1M4, Canada.
Li
A
A
Ni
H
H
Stupack
D G
DG
Shen
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies; D000918:Antibody Specificity; D001667:Binding, Competitive; D016466:CHO Cells; D002448:Cell Adhesion; D002460:Cell Line; D003001:Cloning, Molecular; D003094:Collagen; D006224:Cricetinae; D000939:Epitopes; D005353:Fibronectins; D006801:Humans; D019012:Integrin beta1 / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D015458:Leukemia, T-Cell; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D014162:Transfection; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000939:Epitopes; D005353:Fibronectins; D019012:Integrin beta1; D011994:Recombinant Proteins; D003094:Collagen