Generation of Antibodies to the Urokinase Receptor (uPAR) by DNA Immunization of uPAR Knockout Mice: Membrane‐Bound uPAR is Not Required for an Antibody Response

The urokinase receptor (uPAR) is a glycolipid‐anchored cell surface glycoprotein that plays a central role in extracellular proteolysis during tissue remodeling processes including cancer invasion. Furthermore, uPAR is found on the surface of both dendritic cells (DCs) and T cells, and has been prop...

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Bibliographic Details
Published in:Scandinavian journal of immunology 2003-09, Vol.58 (3), p.298-305
Main Authors: Pass, J., Gårdsvoll, H., Lund, L. R., Danø, K., Høyer‐Hansen, G.
Format: Article
Language:English
Subjects:
Animals
Antibodies - blood
Antibody Formation - genetics
Antibody Formation - immunology
Blotting, Western
Cercopithecus aethiops
COS Cells
Enzyme-Linked Immunosorbent Assay
Female
Genetic Vectors - genetics
Humans
Immunization
Immunoglobulin G - biosynthesis
Immunoglobulin G - classification
Immunoglobulin G - immunology
Mice
Mice, Knockout
Plasmids - genetics
Receptors, Cell Surface - biosynthesis
Receptors, Cell Surface - genetics
Receptors, Cell Surface - immunology
Receptors, Urokinase Plasminogen Activator
Transfection
urokinase receptors
Vaccines, DNA - genetics
Vaccines, DNA - immunology
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Summary:The urokinase receptor (uPAR) is a glycolipid‐anchored cell surface glycoprotein that plays a central role in extracellular proteolysis during tissue remodeling processes including cancer invasion. Furthermore, uPAR is found on the surface of both dendritic cells (DCs) and T cells, and has been proposed to play a role in DC‐induced T‐cell activation and, therefore, in the induction of an immune response. In order to investigate the possibility of using DNA immunization for the generation of poly‐ and monoclonal antibodies to uPAR, we injected wild‐type mice and mice deficient in uPAR (uPAR knockouts) intramuscularly with plasmid DNA encoding a carboxy‐terminal truncated soluble form of the human uPAR. Multiple injections of 100 µg of DNA resulted in a strong and specific antibody response in all mice irrespective of genotype. Antisera with a maximum titre of 32,000 were obtained, comparable with that obtained after immunization with recombinant uPAR. The subclass distribution of uPAR‐specific antibodies in the sera demonstrated the induction of a mixed TH1/TH2 response, irrespective of the genotype of the mice. Our results demonstrate the possibility of generating high titre antibodies to uPAR by DNA immunization of wild‐type as well as uPAR knockout mice, and that cell surface uPAR is not indispensable for the generation of a humoral immune response.
ISSN:0300-9475
1365-3083
DOI:10.1046/j.1365-3083.2003.01299.x