SYNTHESIS AND ASSEMBLY OF MUTANT CONOCLONAL ANTIBODIES

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date1/1/901/1/90

Funding

  • National Institute of Allergy and Infectious Diseases

ASJC

  • Immunology

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