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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
Author(s) -
Pass J.,
Gårdsvoll H.,
Lund L. R.,
Danø K.,
HøyerHansen G.
Publication year - 2003
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.2003.01299.x
Subject(s) - urokinase receptor , antibody , microbiology and biotechnology , receptor , immune system , biology , chemistry , immunology , biochemistry
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 T H 1/T H 2 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.