Cultured hybridoma cells producing monoclonal antibodies will be examined for their ability to generate mutant immunoglobulins with changes in their structure and function. Techniques have been developed to identify such mutants using monoclonals that recognize determinants on the different constant region domains. The frequency of such constant region mutations will be examined in both IgG and IgM producing hybridomas and compared with the frequency of variable region mutations in the same cell lines. Mutant monoclonal antibodies with changes in their intravascular equilibration and decay, in binding to Fc receptors, and in the fixation of complement will be identified and the structural bases of the mutations determined by DNA sequencing. The impact of such somatic mutations in the variable regions on H and L chain compatibility will also be studied. The effectiveness of representative mutant monoclonals in passive immunization and targeting to tumors will be evaluated. It is hoped that these experiments will not only provide insight into the instability of immunoglobulin genes and the structural basis of antibody function, but will also allow us to tailor-make monoclonal antibodies so that they will be more effective diagnostic and therapeutic reagents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI005231-24
Application #
3124227
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1978-09-01
Project End
1988-08-31
Budget Start
1987-09-01
Budget End
1988-08-31
Support Year
24
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
Schools of Medicine
DUNS #
009095365
City
Bronx
State
NY
Country
United States
Zip Code
10461
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