Use of primary sequence information derived from an internal image autoantibody has allowed the identification of the reovirus type 3 cell attachment site. This system provides an opportunity to study the molecular characteristics and functional activities of an anti- lymphocyte autoantibody, similar to those implicated in some autoimmune diseases. Synthetic peptides will be utilized to probe the role of specific amino acid residues involved in contacting the receptor. Site directed mutagenesis of the reovirus type 3 hemagglutinin (HA3) cDNA will be carried out in this region to confirm and extend these results. Binding to the reovirus type 3 receptor (Reo3R), as well as to a neutralizing anti-reovirus type 3 monoclonal antibody (9BG5) which binds the cell attachment site of the virus, will be studied. These studies will allow molecular characterization of autoantibody mimicry of a viral cell attachment site. The neutralizing monoclonal antibody 9BG5, which binds both reovirus type 3 and the autoantibody 87.92.6, will also be studied. Determination of the nucleotide and deduced amino acid sequences of 9BG5 will allow the development of synthetic peptide analogs of its binding site. These peptides can be utilized in a series of studies to investigate the various interactions between reovirus type 3, idiotype (9BG5), anti-idiotypic autoantibody, and the Reo3R. This will allow the molecular characterization of the interactions inherent in the development of anti-idiotypic autoantibodies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29AI028503-04
Application #
3455260
Study Section
Immunobiology Study Section (IMB)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104