Tumor cells from a UV-induced C3H fibrosarcoma express a multiplicity of unique tumor-specific antigens. These products, defined by cloned T-cell lines, appear to play an important role in the immune response of the host to the tumor. Using monoclonal antibodies with unique specificity for this tumor, several of these antigens have recently been characterized as bona fide transplantation antigens alien to the C3H mouse. We have cloned and sequenced the genes encoding these novel transplantation antigens to establish the genetic basis for their anomalous expression; i.e., their multiplicity and uniqueness. The class I genes--polymorphic to their counterparts from normal tissues--are altered by what appear to represent somatic recombination levels between class I sequences. Manifested as the insertion of small sets of sequences as--one class I comes into another, these recombination events produce the restriction enzyme site polymorphisms in the class I genes of tumor versus normal DNA. Southern blot hybridization analysis of the class I genes of other murine tumors (e.g., myelomas, lymphomas) has also revealed tumor-specific class I polymorphism to suggest a link between neoplasia and class I alterations. Thus, the molecular analysis of the class I genes in tumors may elucidate a role for class I gene rearrangements in the immune response to malignant diseases. The molecular cloning of these genes should provide unique opportunities to study the relationship between the class I diversification and the immunopathology of this neoplastic disease. This research work is submitted as a companion to that of Dr. Hans Schreiber on the immunobiology of these tumor-specific unique MHC antigens. (AG)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037099-03
Application #
3174786
Study Section
Immunobiology Study Section (IMB)
Project Start
1984-03-01
Project End
1987-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
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