Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.
IMMUNOLOGIC STUDIES OF THE SURFACE ANTIGENS OF NORMAL AND NEOPLASTIC MURINE LYMPHOCYTES
Diss Abstr Int [B]; 49(9):3666 1989. Unique Identifier : AIDSLINE ICDB/90657008 Pillemer EA; Stanford Univ., CA
Abstract:
The research presented in this thesis was designed to identify (1) T-lymphocyte surface molecules involved in target recognition and (2) tumor surface antigens involved in tumor rejection and/or tumor growth. In the first series of experiments, a panel of rat monoclonal antibodies was prepared against the AKR T lymphoma KKT-2. One antibody was found to bind to the Thy-1 antigen on all murine T lymphocytes, as well as to an idiotypic determinant on the TEPC-15 myeloma protein. Anti-Thy-1, anti-Lyt-1, and anti-Lyt-2 antibodies were added to mixed lymphocyte cultures (MLC) and mitogen-stimulated T cells. Anti-Lyt-2 antibodies strongly inhibited MLC, while anti-Lyt-1 was stimulatory. Anti-Thy-1 did not affect MLC, but blocked mitogen-induced proliferation, suggesting a possible role for the Thy-1 antigen in T-cell activation. The anti-KKT-2 antibodies were next screened against a panel of virally infected cells and purified viruses. One antibody (43-17) detects a determinant on the leader or L peptide of the cell surface glycosylated gag polyproteins of endogenous murine leukemia viruses. Using the 43-17 antibody, it was shown that the gag polyproteins are anchored to the cell membrane via the hydrophobic amino terminus containing the L peptide. Moloney-type virus gag polyproteins lack the L peptide and thus do not express high levels of the cell surface gag polyproteins. In separate experiments, cytolytic T-cell clones were generated against the Abelson leukemia virus (AbLV) transformed pre-B cell lymphoma L1-2. One clone (1E4) was found to mediate tumor rejection in genetically susceptible mice inoculated with a lethal dose of L1-2 cells. The 1E4 clone was used to immunize rats to prepare monoclonal antibodies to cytolytic T cells. One antibody (6C3) was found to bind the L1-2 target cells rather than 1E4. This antibody is directed against a cell surface molecule on AbLV-transformed cells which is unrelated to any AbLV-encoded protein, but which correlates closely with acquisition of the fully transformed phenotype in in vitro bone marrow cultures infected with AbLV. (Full text available from University Microfilms International, Ann Arbor, MI, as Order No. AAD88-26213)
Keywords: Animal Antibodies, Monoclonal/DIAGNOSTIC USE Antigens, Surface/*IMMUNOLOGY Antigens, Viral/IMMUNOLOGY Cell Transformation, Neoplastic/*IMMUNOLOGY Cell Transformation, Viral Comparative Study Gene Products, gag/IMMUNOLOGY Leukemia Viruses, Murine/IMMUNOLOGY Mice Signal Peptides/IMMUNOLOGY T-Lymphocytes/*IMMUNOLOGY Tumor Cells, Cultured/IMMUNOLOGY THESIS 900228
M9020587
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