Abstract
Syngenic C57BL/6 mice (H-2(b)) vaccinated with mitomycin C-treated L12R4 T lymphoma cells develop protective immunity toward the MHC class II-negative tumor cells. In the present study, we characterize the nature, mode of function, and specificity of the effector cells in this immunity. These cells are TCR-specific CD8(+) T lymphocytes with effector function in vitro as well as in vivo upon transfer to naive mice. They produce high levels of IFN-gamma and TNF-alpha, but little or no IL-4. By means of TCRbeta-negative variant L12R4 cells, P3.3, and TCR-Vbeta2 cDNA-transfected and TCR-Vbeta2-expressing P3.3 lymphoma cells, we found that a significant part of the effector T cells are specific for the Vbeta12 region. The growth inhibition of L12R4 cells in vitro was inhibited by anti-H-2, anti-K(b), and anti-D(b) mAb. Furthermore, vaccination with Vbeta12 peptide p67-78, which binds to both K(b) and D(b) MHC class I molecules, induces partial protection against L12R4 T lymphoma cells. Thus, self-reactive TCR-Vbeta-specific, K(b)-, or D(b)-restricted CD8(+) T cells mediate inhibition of T cell lymphoma growth in vitro and in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Autoantigens / immunology*
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Autoantigens / metabolism
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / transplantation
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Cell Line, Tumor
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Cell Proliferation*
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Cytotoxicity Tests, Immunologic
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Cytotoxicity, Immunologic*
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Epitopes, T-Lymphocyte / immunology
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Immunity, Innate
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Immunodominant Epitopes / immunology
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Immunodominant Epitopes / metabolism
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Immunotherapy, Adoptive / methods
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Interferon-gamma / deficiency
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Interferon-gamma / genetics
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Interferon-gamma / physiology
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Leukemia L1210
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Lymphoma, T-Cell / immunology
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Lymphoma, T-Cell / pathology*
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Lymphoma, T-Cell / prevention & control*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Neoplasm Transplantation
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Receptors, Antigen, T-Cell, alpha-beta / immunology*
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Regulatory / immunology
Substances
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Autoantigens
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Epitopes, T-Lymphocyte
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Immunodominant Epitopes
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Receptors, Antigen, T-Cell, alpha-beta
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Interferon-gamma