The overall goal of this project is to study how cytotoxic T lymphocytes (CTL) recognize antigens on the surface of SV4O-transformed mouse cells. The technique of growing effector lymphocytes at clonal levels, together with the use of H-2 variants and SV40 deletion mutants produced by gene manipulation, provides a powerful tool to elucidate the immune recognition of SV40-transformed cells by H-2-restricted CTL. We intend to identify the region(s) of the class I H-2 antigen-restricting element using H-2K?b?-restricted CTL cloned cell lines and a target cell panel consisting of the spontaneously arising K mutants and a series of chemically induced somatic cell variants with altered K?b?. These new K?b? somatic cell variants have been partially characterized with a series of monoclonal anti-K?b? antibodies and their genomic DNA is being sequenced. We also intend to map the portion(s) of the SV40 T antigen which is expressed on the cell surface and is immunologically recognized. In this work, we will make use of monoclonal antibodies, which will be mapped to distinct epitopes of the SV40 T molecule and a transforming SV40 deletion mutant which produces truncated T antigens. We will continue to produce monoclonal antibodies to mouse SV40 transformants to optimize chances of obtaining relevant antibodies that detect T antigens on the SV40-transformed cell surface. This structure-function analysis is designed to provide information about the immune recognition of SV40 TSTA and the involvement of H-2 in CTL recognition and may ultimately lead to methods of manipulating the host immune response to control tumor growth. (AG)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037303-02
Application #
3175132
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-05-01
Project End
1987-04-30
Budget Start
1985-05-01
Budget End
1986-04-30
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Wistar Institute
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Pan, S; Abramczuk, J; Knowles, B B (1987) Immune control of SV40-induced tumors in mice. Int J Cancer 39:722-8
Pan, S; Doherty, P J (1986) The use of spun columns in the purification of double-stranded cDNA appropriate for tailing. Anal Biochem 156:305-6
Chang, L S; Pan, S; Pater, M M et al. (1985) Differential requirement for SV40 early genes in immortalization and transformation of primary rat and human embryonic cells. Virology 146:246-61
Pan, S; Sompayrac, L M; Knowles, B B et al. (1985) A fragment of the simian virus 40 early genome can induce tumors in nude mice. J Virol 53:988-9