Dissecting the Immunogenicity of Monoclonal Antibodies
Abstract
The potential of mononclonal antibodies, (mAbs), for use in therapeutic and diagnostic applications has not been fully realized in part due to counter-immune responses that often arise in patient recipients of mAb. A growing research effort to humanize mAb has focused primarily on the structure or sequence of the antibody variable (V) region domains. However, these approaches may ultimately suffer, as they overlook the requirement of T cell help for the immune counter-reaction and the potential of somatic hypermutation and V-D-J recombination to generate target T cell epitopes within mAb V regions. My approach focuses on this issue. In order to understand some basic principals concerning anti-immunoglobulin immune responses, I have developed methods, reagents and mouse strains during the previous funding year to effectively study T cell epitopes in mAb V regions. I was able to reproducibly distinguish an immune response to a V-region T cell epitope via a lymph node proliferation assay. Furthermore, I have generated MHC-tetrameric staining reagents with which I can identify T cells reactive with two such epitopes. Finally, I have generated congenic mouse strains containing or lacking the enzyme terminal deoxynucleotidyl transferase, (TdT), in order to address the role of T cell epitopes in junctional diversity.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA396678
Entities
People
- Christopher M Snyder
- Lawrence J. Wysocki
Organizations
- National Jewish Health