1994 Fiscal Year Final Research Report Summary
Identification of non-mutated c-erbB-2 derived peptides recognized by murine CD8+ cytotoxic T cells
| Project/Area Number |
05807113
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | Nagasaki University school of Medicine |
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Principal Investigator |
KOHARA Norihiro Nagasaki University School of Medicine Lecturer, 医学部, 講師 (40221238)
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| Co-Investigator(Kenkyū-buntansha) |
SHIKU Hiroshi Nagasaki University School of Medicine Professor, 医学部, 教授 (80154194)
KANEMATSU Takashi Nagasaki University School of Medicine Professor, 医学部, 教授 (40128004)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Oncogene / Cytotoxic T Lymphocytes / Peptide Antigen / Tumor Antigen |
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| Research Abstract |
Expression of a variety of proto-oncogenes is often enhanced in cancer tissues. This indicates that peptides derived from proto-oncogenes are possible candidates as targets for immunoprotection against cancer. In many instances however, they are non-mutated and therefore not cancer specific in the strict sense. In fact most wild type proto-oncogenes are expressed in normal tissues to variable extends. This prompted us to investigate whether nonmutated peptides of the proto-oncogene c-erbB-2 can be recognized by murine cytotoxic T cells (CTL).
BALB/c mice immunized with CMS17HE (a syngeneic fibrosarcoma line transfected with human c-erbB-2 c-DNA), but not with CMS17neo or CMS17 rejected another syngeneic sarcoma line transfected with human c-erbB-2, CMS7HE.Spleen cells from thus immunized mice were further sensitized in vitro with CMS17HE.They became cytotoxic for transfectants of human and murine c-erbB2(CMS7HE and CMS7ME), but not parental CMS7 and CMS7neo.
The activity was blocked by monoclonal antibodies for murine CD8^+ or K^d, but not for CD4^+, D^d, I-A^d. These CTL were reactive with L-cells (H-2^k) transfected with Kd and c-erbB-2 cDNA,and also SK-Br3, a human breast cancer line expressing c-erbB-2, transfected with K^d cDNA.A series of peptides opf human or murine c-erbB-2 compatible with the K^d motif was synthesized. The CTL were reactive with P1HTR( H-2^d) pulsed with three peptides, CP811-1 (T) (human c-erbB-2 derived), CP811-1 (A) (murine c-erbB-2 derived), and CP811-5(common for human and murine c-erbB-2). Spleen cells immunized in vivo and in vitro with syngeneic spleen cells pulsed with these peptides were cytotoxic for CMS17HE and/or CMS17ME.
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