The overall goal of this project is further characterization of the surface proteins of the Lyme disease agent, Borrelia burgdorferi sensu lato, and the interface between those proteins and the host's immune response, specifically antibodies.
The aims for this project are following: (I) To evaluate the variety and specificities of bactericidal antibodies to B. burgdorferi. This will be accomplished: (a) by producing and selecting other bactericidal antibodies from mice and humans using hybridoma technology and combinatorial immunoglobulin gene libraries in filamentous bacteriophage, and (b) by determining the epitopes for these antibodies. (II) To determine the mechanism of complement- independent bactericidal activity of antibodies to borrelias. This will be accomplished by (a) documenting the course and distribution of antibody binding to the cells, (b) assessing the environmental variables in bacterial cell death consequent to antibody binding, (c) determining if autolysis and other disturbances of macromolecular synthesis occurs after antibody binding, and (d) carrying out biophysical analysis of the Osp proteins and their interactions with antibody. (III) To further define the structure and membrane topology of the protein surface antigens of B. burgdorferi. This will be accomplished by (a) producing escape mutants with human antisera to recombinant OspA, (b) determining the mechanism of antibody resistance of mutants that retain the linear epitope for the selecting antibody, and (c) carrying out various studies of the physical associations between Osp proteins in the outer membrane.
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