1995 年度実績報告書

がん抗原分子と免疫認識

研究課題

研究課題/領域番号	06282103
研究機関	千葉大学
研究代表者	谷口克千葉大学, 医学部, 教授 (80110310)
研究分担者	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)
キーワード	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
研究概要	1.MHC結合ペプチドモチーフ: イ.クラスIMHC(HLA-B3501など)結合ペプチドを分離し、シークエンス解析から16種類のペプチドのモチーフを明らかにした。その結果、これまで知られていなかったペプチド部分もMHCとの結合に重要であることが明らかとなった。さらに、これらをもとに、C型肝炎ウイルスのCTLエピトープが同定できた。ロ.MHC結合がん抗原ペプチドを同定するためには、CTLクローンの確立が必要であるが、子宮癌、メラノーマ(タイロシネース)特異的なCTLクローンの確立に成功した。それを用いてがん抗原ペプチド画分を特定することに成功した。ハ.一方、hsp70はがん抗原ペプチドをユビキチン・プロテオゾームとTAP-ER間の輸送を司る分子であることが証明された。 2.がん抗原とCTLエピトープ: ウイルス誘発白血球抗原のCTLエピトープを合成ペプチドを用いて同定した。驚くべきことにそれはFVgag前駆体の9個のリーダー配列のものががん抗原として機能していることを証明した点で極めて特異である。昨年での成果でもこれと別の系で同様のことが証明されているのでこの知見は極めて重要な知見と思われる。 3.腫瘍内浸潤Tリンパ球(TIL): 原発巣と転移巣のTILのレパートリーは全く異なり、決してオーバーラップすることは無い。しかも、2-3のT細胞クローンのみが増殖していることが判明し、特異な免疫反応状態にあることを示した。一方、TIL(CTL)の腫瘍内へのtrafficには、IL-12が重要な働きをする事。IL-12によってTIL(CTL)のγ-IFN産生が亢進し、腫瘍増殖抑制を導くことを明らかにした。

研究成果

(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] Wang. R. -F.: "Limited T cell antigen receptor repertoire in tumorinfiltrating lymphocyte and inhibition of experimental lung metastasis of murine melanoma by anti-TCR antibody." J. Immunol.154. 1797-1803 (1995)
[文献書誌] Taniguchi, M.: "Restricted TCR repertoire in TIL of metastatic lung melanoma." Excerpta Medica. (in press.).
[文献書誌] Mu, J.: "Administeation of rlL-12 prevents outgrowth of tumor cells metastasizing spontaneously to lung and lymph nodes." Cancer Res.55. 4404-4408 (1995)
[文献書誌] Zou, J. -P.: "Systemic administration of rlL-12 induces complete tumor regression and protective immunity: Response is corelated with a striking reversal of suppressed interferon-γ production by anti-tumor T cells." Int. Immunol.7. 1135-1145 (1995)
[文献書誌] Takamiya, K.: "T cell receptor-mediated stimulation if mouse thymocytes induces up-regulation of the GM2-GD2 synthase gene." FEBS Lett.358. 79-83 (1995)
[文献書誌] Yamashiro, A.: "Substrate specificity of β 1,4 N-acetyl-galacto-saminyl transferase in vitro and in cDNA-transfected cella. GM2/GD2 synthase efficiently generates asialo-GM2 in certain cells." J. Biol. Chem.270. 6149-6155 (1995)
[文献書誌] Sonoda, K.: "Establishment of a new human uterine adenocarcioma cell line, Siso, and its reactivity to anti-cancer reagent." Intl. J. Oncology. 6. 1009-1104 (1995)
[文献書誌] Futaki, G.: "Naturally processed HLA-DR9/DR53(DRBI^*0901/DRB4^*0101)-bound peptids." Immunogenetics. 42. 299-301 (1995)
[文献書誌] Kobayashi, H.: "Analysis of naturally processed human histo-compatibility leukocyte antigen Class I-bound peptides from hepatocellular carcinoma tissues in vivo." Jpn. J. Cancer Res.86. 962-968 (1995)
[文献書誌] Kannagi, M.: "Cytotoxic T cell response and expression of the target antigen in HTLV-I infection." Leukemia.8. 54-59 (1995)
[文献書誌] Kannagi, M.: "Expression of the target antigen for cytotoxic T lymphocytes on adult T cell leukemia cells." Int. J. Cancer. 54. 582-588 (1993)
[文献書誌] Takahima, S.: "Mechanism ofinteraction between 70KDa heat shock proteins and rat CD3^+4^-8^- killer T cells -implication in the tumor rejection activity." Transplant. Proc.27. 1507-1508 (1995)
[文献書誌] Inoue, A.: "70kDa heat shock cognate protein interacts directly with the N-terminal region of the retinoblastoma gene product pRb-Identification of a novel region of prb mediating protein interaction." J. Biol. Chem.270. 22571-22576 (1995)
[文献書誌] Kondo, T.: "A Singie retroviral gas precursor signal peptide recognized by FBL-3-tumor-specific cytotoxic T lymphocytes." J. Virol.69. 6735-6741 (1995)
[文献書誌] Miyazawa, M,: "Immunization with a single T helper cell epitope abrogtes Friend virus-induced early erythroid proliferation and prevent late leukemia development." J. Immunol.155. 748-758 (1995)
[文献書誌] Ichihara, M.: "Oncogene-linked in situ immuno-therapy of pre-B lymphoma arising in Eu/ret transgenic mice." Brit. J. Cancer. 71. 808-813 (1995)
[文献書誌] Dai, Y.: "Recombinant ret oncogene product induced T lymphocyte proliferation, which suppressed lymphoma derived from ret transgenic mice." Int. J. Oncology. 5. 661-665 (1994)
[文献書誌] Sochonbach, C.: "Fine turning of peptide binding to HLA-B^*3501 molecules by nonanchor residues." J. Immunol.154. 5951-5958 (1995)
[文献書誌] Shindy, J.: "Several HILA alleles share overlapping peptide specificities." J. Immunol.154. 247-259 (1995)

1995 年度 実績報告書

がん抗原分子と免疫認識

研究代表者

谷口 克 千葉大学, 医学部, 教授 (80110310)

研究成果

[文献書誌] Wang. R. -F.: "Limited T cell antigen receptor repertoire in tumorinfiltrating lymphocyte and inhibition of experimental lung metastasis of murine melanoma by anti-TCR antibody." J. Immunol.154. 1797-1803 (1995)

[文献書誌] Taniguchi, M.: "Restricted TCR repertoire in TIL of metastatic lung melanoma." Excerpta Medica. (in press.).

[文献書誌] Mu, J.: "Administeation of rlL-12 prevents outgrowth of tumor cells metastasizing spontaneously to lung and lymph nodes." Cancer Res.55. 4404-4408 (1995)

[文献書誌] Zou, J. -P.: "Systemic administration of rlL-12 induces complete tumor regression and protective immunity: Response is corelated with a striking reversal of suppressed interferon-γ production by anti-tumor T cells." Int. Immunol.7. 1135-1145 (1995)

[文献書誌] Takamiya, K.: "T cell receptor-mediated stimulation if mouse thymocytes induces up-regulation of the GM2-GD2 synthase gene." FEBS Lett.358. 79-83 (1995)

[文献書誌] Yamashiro, A.: "Substrate specificity of β 1,4 N-acetyl-galacto-saminyl transferase in vitro and in cDNA-transfected cella. GM2/GD2 synthase efficiently generates asialo-GM2 in certain cells." J. Biol. Chem.270. 6149-6155 (1995)

[文献書誌] Sonoda, K.: "Establishment of a new human uterine adenocarcioma cell line, Siso, and its reactivity to anti-cancer reagent." Intl. J. Oncology. 6. 1009-1104 (1995)

[文献書誌] Futaki, G.: "Naturally processed HLA-DR9/DR53(DRBI^*0901/DRB4^*0101)-bound peptids." Immunogenetics. 42. 299-301 (1995)

[文献書誌] Kobayashi, H.: "Analysis of naturally processed human histo-compatibility leukocyte antigen Class I-bound peptides from hepatocellular carcinoma tissues in vivo." Jpn. J. Cancer Res.86. 962-968 (1995)

[文献書誌] Kannagi, M.: "Cytotoxic T cell response and expression of the target antigen in HTLV-I infection." Leukemia.8. 54-59 (1995)

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

[文献書誌] Takahima, S.: "Mechanism ofinteraction between 70KDa heat shock proteins and rat CD3^+4^-8^- killer T cells -implication in the tumor rejection activity." Transplant. Proc.27. 1507-1508 (1995)

[文献書誌] Inoue, A.: "70kDa heat shock cognate protein interacts directly with the N-terminal region of the retinoblastoma gene product pRb-Identification of a novel region of prb mediating protein interaction." J. Biol. Chem.270. 22571-22576 (1995)

[文献書誌] Kondo, T.: "A Singie retroviral gas precursor signal peptide recognized by FBL-3-tumor-specific cytotoxic T lymphocytes." J. Virol.69. 6735-6741 (1995)

[文献書誌] Miyazawa, M,: "Immunization with a single T helper cell epitope abrogtes Friend virus-induced early erythroid proliferation and prevent late leukemia development." J. Immunol.155. 748-758 (1995)

[文献書誌] Ichihara, M.: "Oncogene-linked in situ immuno-therapy of pre-B lymphoma arising in Eu/ret transgenic mice." Brit. J. Cancer. 71. 808-813 (1995)

[文献書誌] Dai, Y.: "Recombinant ret oncogene product induced T lymphocyte proliferation, which suppressed lymphoma derived from ret transgenic mice." Int. J. Oncology. 5. 661-665 (1994)

[文献書誌] Sochonbach, C.: "Fine turning of peptide binding to HLA-B^*3501 molecules by nonanchor residues." J. Immunol.154. 5951-5958 (1995)

[文献書誌] Shindy, J.: "Several HILA alleles share overlapping peptide specificities." J. Immunol.154. 247-259 (1995)

1995 年度実績報告書

谷口克千葉大学, 医学部, 教授 (80110310)

[文献書誌] Futaki, G.: "Naturally processed HLA-DR9/DR53(DRBI^0901/DRB4^0101)-bound peptids." Immunogenetics. 42. 299-301 (1995)