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Identification of Meth A sarcoma-derived class I major histocompatibility complex-associated peptides recognized by a specific CD8+ cytotoxic T lymphocyte. 1995

M A Frassanito, and J I Mayordomo, and R M DeLeo, and W J Storkus, and M T Lotze, and A B DeLeo
Pittsburgh Cancer Institute, Division of Basic Research, Pennsylvania 15261.

The finding that class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) recognize peptide antigens (epitopes) bound to class I MHC molecules has accelerated efforts to identify CTL-defined tumor peptides for the development of peptide-based cancer immunotherapy. The Meth A sarcoma is probably one of the best studied of all murine tumors. It is extremely lethal unless protective immunity is induced. We recently reported the characterization of a cloned H-2Kd-restricted, CD8+ anti-Meth A CTL line (CTLMA-9C; Frassanito et al., Cancer Res., 54: 4424-4429, 1994). The cytotoxic reactivity of this CTL was shown to be restricted to Meth A sarcoma, and the results of the analysis of the immunogenicity of the CTL-resistant variant of Meth A, designated Meth A4R, indicate that the CTL-defined epitope is functional in tumor rejection. Here we have isolated class I MHC-associated peptides from Meth A sarcoma by mild acid treatment and resolved them into sixty fractions by reverse phase-HPLC. These fractions were then tested for their ability to sensitize the DBA/2 mastocytoma P815 to cytolysis by the anti-Meth A CTL. A single fraction, fraction 27, has been repeatedly identified as containing the CTL-defined epitope. Peptides eluted from the CTL-resistant variant, Meth A4R, failed to sensitize P815 to cytolysis by the anti-Meth A CTL, while fraction 27 derived from Meth A sensitized Meth A4R to lysis by the CTL. These findings confirm the peptide nature of the epitope recognized by CTL on the surface of Meth A. Our future efforts will focus on the identification and sequence analysis of the tumor peptides and the development of a tumor peptide-based vaccine model for immunotherapy.

UI MeSH Term Description Entries
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008811 Mice, Inbred DBA An inbred strain of mouse. Specific substrains are used in a variety of areas of BIOMEDICAL RESEARCH such as DBA/1J, which is used as a model for RHEUMATOID ARTHRITIS. Mice, DBA,Mouse, DBA,Mouse, Inbred DBA,DBA Mice,DBA Mice, Inbred,DBA Mouse,DBA Mouse, Inbred,Inbred DBA Mice,Inbred DBA Mouse
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003601 Cytotoxicity Tests, Immunologic The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement. AHG-CDC Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Tests,Microcytotoxicity Tests,Anti Human Globulin Complement Dependent Cytotoxicity Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunologic,Cytotoxicity Tests, Anti-Human Globulin Complement-Dependent,Cytotoxicity Tests, Immunological,Immunologic Cytotoxicity Test,Immunologic Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin-Augmented,Lymphocytotoxicity Tests, Antiglobulin-Augmented,Microcytotoxicity Test,AHG CDC Tests,AHG-CDC Test,Anti Human Globulin Complement Dependent Cytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunological,Cytotoxicity Tests, Anti Human Globulin Complement Dependent,Immunological Cytotoxicity Test,Immunological Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin Augmented,Lymphocytotoxicity Tests, Antiglobulin Augmented
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000939 Epitopes Sites on an antigen that interact with specific antibodies. Antigenic Determinant,Antigenic Determinants,Antigenic Specificity,Epitope,Determinant, Antigenic,Determinants, Antigenic,Specificity, Antigenic
D000951 Antigens, Neoplasm Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin. Neoplasm Antigens,Tumor Antigen,Tumor Antigens,Antigen, Tumor,Antigens, Tumor
D012513 Sarcoma, Experimental Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA. EHS Tumor,Sarcoma, Engelbreth-Holm-Swarm,Sarcoma, Jensen,Experimental Sarcoma,Experimental Sarcomas,Sarcomas, Experimental,Engelbreth-Holm-Swarm Sarcoma,Jensen Sarcoma,Sarcoma, Engelbreth Holm Swarm,Tumor, EHS
D012515 Mast-Cell Sarcoma A unifocal malignant tumor that consists of atypical pathological MAST CELLS without systemic involvement. It causes local destructive growth in organs other than in skin or bone marrow. Mastocytoma, Malignant,Sarcoma, Mast-Cell,Malignant Mastocytoma,Malignant Mastocytomas,Mast Cell Sarcoma,Mast-Cell Sarcomas,Mastocytomas, Malignant,Sarcoma, Mast Cell,Sarcomas, Mast-Cell
D013602 T-Lymphocytes, Cytotoxic Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2. Cell-Mediated Lympholytic Cells,Cytotoxic T Cells,Cytotoxic T Lymphocyte,Cytotoxic T-Lymphocytes,TC1 Cell,TC1 Cells,TC2 Cell,TC2 Cells,Cell Mediated Lympholytic Cells,Cell, Cell-Mediated Lympholytic,Cell, TC1,Cell, TC2,Cell-Mediated Lympholytic Cell,Cytotoxic T Cell,Cytotoxic T Lymphocytes,Cytotoxic T-Lymphocyte,Lymphocyte, Cytotoxic T,Lympholytic Cell, Cell-Mediated,Lympholytic Cells, Cell-Mediated,T Cell, Cytotoxic,T Lymphocyte, Cytotoxic,T Lymphocytes, Cytotoxic,T-Lymphocyte, Cytotoxic

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