1994 Fiscal Year Annual Research Report

がん抗原分子と免疫認識

Research Project

Project/Area Number	06282103
Research Category	Grant-in-Aid for Scientific Research on Priority Areas
Research Institution	Chiba University
Principal Investigator	谷口克千葉大学, 医学部, 教授 (80110310)
Co-Investigator(Kenkyū-buntansha)	渡辺武九州大学, 生体防御医学研究所, 教授 (40028684) 中島泉名古屋大学, 医学部, 教授 (40022826) 佐藤昇志札幌医科大学, 医学部, 教授 (50158937) 古川鋼一長崎大学, 医学部, 助教授 (80211530) 栗林景容三重大学, 医学部, 教授 (10064578)
Keywords	がん抗原 / MHCペプチド / キラーT細胞 / TIL / T細胞エピトープ / T細胞レパトア / クラスIMHC / ペプチドモチーフ
Research Abstract	1.ヒトおよびマウス腫瘍細胞を可溶化し、免疫沈降法を用いてMHC分子を単離・精製した。さらにMHC分子よりMHC結合ペプチドを酸で抽出し、ゲル濾過によって分画した。各分画中のペプチドをMHC分子に再結合させ、腫瘍特異的キラーT細胞活性が検出されているか否かでがん抗原ペプチドの同定を行った。その結果、マウス白血病がん抗原がプロテインキナーゼcの一つであるc-aktの非翻訳部分であることを同定した。これを人工合成したペプチドを免役することによって、マウス白血病細胞を把握したことから、これが腫瘍抗原ペプチドとして同定された世界で初めての例となった。その他、ヒトおよびマウス由来のMHC結合ペプチドを同定できた。さらにヒトMHC結合ペプチド同定に必須なCTL株を効率よく樹立する方法を確立した。 2.がん抗原の決定は、上記方法とは別に遺伝子導入、合成ペプチドによるエピトープマップでも行われウイルス性抗原、がん遺伝子、ガングリオシド、熱たんぱくにがん抗原性が存在することを見い出した。 3.坦がん生体は通常反応が抑制されている。したがって、免疫でのがん治療を困難なものにしている。その原因の一つが抑制T細胞によることを、in vivo レベルで証明できた。すなわち、遺伝子レベルでのTILの受容体の解析からTILレパトアは極めて限られており、抗受容体抗体を用いることによって抑制T細胞を除去することによってがん転移の抑制が出来た。

Research Products

(15 results)

All Other

All Publications (15 results)

[Publications] Wang,R.-f.: "Limited T cell antigen recepter repertoire in TIL and prevention of experimental lung metastasis of murine melanoma by anti-TCR antibody." J.Immunol.(in press).
[Publications] iakamiya,Y.: "HLA-B^1 3501-peptide interactions: Role of anchor residues of peptides in their binding to HLA-B^X 3501 molecules." Int. Immunol.6. 255-261 (1994)
[Publications] Falk,K.: "Peptide motifs of HLA-Al, -All, -A31 and -A33 and molecules." Immunogenetics. 40. 238-241 (1994)
[Publications] Kinouchi,R.: "Peptide motifs of HLA-DR4/DR53(DRB1^Z0405/DRB4^Z0101) molecules." Immunogenetics. 40. 376-378 (1994)
[Publications] Uenaka,A.: "Identification of a unique antigen peptide pRL1 on BALB/c RL ♂1 leukemia recognized by cytotoxic T-lymphocytes and its relation to the Akt oncogene." J.Exp.Med.180. 1599-1607 (1994)
[Publications] Shimizu,M.: "Fine structure of a virus-encoded helper T cell epitope expressed on FBL-3 tumor cells." J.Virol.68. 7704-7008 (1994)
[Publications] Nakashima,M.: "In vitro expansion of melanoma specific, HLA restricted CD8+ cytotoxic T lymphocytes." Cellular Immunol.155. 53-61 (1994)
[Publications] Sakashima,S.: "Mechanism of interaction between 70KDa heat shock proteins and rat CD3+4-8- killer T cells implication in the tumor rejection activity." Transpl.Proc.(in press).
[Publications] Inoue,A.: "70kDa heat shock cognate protein directly interacts with N-terminal region of the retinoblastoma gene product pRb identification of a novel region of pRb mediating protein interaction." J.Biol.Chem.(in press).
[Publications] Tamura,Y.: "70kDa heat shock cognate protein is a transformation-associated antigen and a possible target for the host's antitumor immunity." J.Immunol.151. 5516-5524 (1994)
[Publications] Kannagi,M.: "Expression of the target antigen for cytotoxic T lymphocytes on adult T cell leukemia cells." Int.J.Cancer. 54. 582-588 (1993)
[Publications] Yamamoto,N.: "Regulatory mechanisms for production of interferon-γ and tumor necrosis factor by anti-tumor T cells or macrophages in the tumor-bearing state." J.Immunol.(in press).
[Publications] Yan,D.: "Recombinant ret oncogene products induce T lymphocyte proliferation, and suppress lymphoma derived from ret transgenic mice." Int.J.Oncology. 5. 661-665 (1994)
[Publications] Haraguchi,M.: "Isolation of GD3 synthase gene by expression cloning of GM3 α2,8-sialytransferase cDNA using anti-GD2 monoclonal antibody." Proc.Natl.Acad.Sci.USA. 91. 10455-10459 (1994)
[Publications] Yamashiro,A.: "Substrate specificity of β1,4 N-acetylgalactosaminyl transferease in vitro and in cDNA-transfected cells. GM2/GD2 synthase efficiently generates asialo-GM2 in certa-in cells." J.Biol.Chem.(in press).

1994 Fiscal Year Annual Research Report

がん抗原分子と免疫認識

Principal Investigator

谷口 克 千葉大学, 医学部, 教授 (80110310)

Research Products

[Publications] Wang,R.-f.: "Limited T cell antigen recepter repertoire in TIL and prevention of experimental lung metastasis of murine melanoma by anti-TCR antibody." J.Immunol.(in press).

[Publications] iakamiya,Y.: "HLA-B^1 3501-peptide interactions: Role of anchor residues of peptides in their binding to HLA-B^X 3501 molecules." Int. Immunol.6. 255-261 (1994)

[Publications] Falk,K.: "Peptide motifs of HLA-Al, -All, -A31 and -A33 and molecules." Immunogenetics. 40. 238-241 (1994)

[Publications] Kinouchi,R.: "Peptide motifs of HLA-DR4/DR53(DRB1^Z0405/DRB4^Z0101) molecules." Immunogenetics. 40. 376-378 (1994)

[Publications] Uenaka,A.: "Identification of a unique antigen peptide pRL1 on BALB/c RL ♂1 leukemia recognized by cytotoxic T-lymphocytes and its relation to the Akt oncogene." J.Exp.Med.180. 1599-1607 (1994)

[Publications] Shimizu,M.: "Fine structure of a virus-encoded helper T cell epitope expressed on FBL-3 tumor cells." J.Virol.68. 7704-7008 (1994)

[Publications] Nakashima,M.: "In vitro expansion of melanoma specific, HLA restricted CD8+ cytotoxic T lymphocytes." Cellular Immunol.155. 53-61 (1994)

[Publications] Sakashima,S.: "Mechanism of interaction between 70KDa heat shock proteins and rat CD3+4-8- killer T cells implication in the tumor rejection activity." Transpl.Proc.(in press).

[Publications] Inoue,A.: "70kDa heat shock cognate protein directly interacts with N-terminal region of the retinoblastoma gene product pRb identification of a novel region of pRb mediating protein interaction." J.Biol.Chem.(in press).

[Publications] Tamura,Y.: "70kDa heat shock cognate protein is a transformation-associated antigen and a possible target for the host's antitumor immunity." J.Immunol.151. 5516-5524 (1994)

[Publications] Kannagi,M.: "Expression of the target antigen for cytotoxic T lymphocytes on adult T cell leukemia cells." Int.J.Cancer. 54. 582-588 (1993)

[Publications] Yamamoto,N.: "Regulatory mechanisms for production of interferon-γ and tumor necrosis factor by anti-tumor T cells or macrophages in the tumor-bearing state." J.Immunol.(in press).

[Publications] Yan,D.: "Recombinant ret oncogene products induce T lymphocyte proliferation, and suppress lymphoma derived from ret transgenic mice." Int.J.Oncology. 5. 661-665 (1994)

[Publications] Haraguchi,M.: "Isolation of GD3 synthase gene by expression cloning of GM3 α2,8-sialytransferase cDNA using anti-GD2 monoclonal antibody." Proc.Natl.Acad.Sci.USA. 91. 10455-10459 (1994)

[Publications] Yamashiro,A.: "Substrate specificity of β1,4 N-acetylgalactosaminyl transferease in vitro and in cDNA-transfected cells. GM2/GD2 synthase efficiently generates asialo-GM2 in certa-in cells." J.Biol.Chem.(in press).

谷口克千葉大学, 医学部, 教授 (80110310)