1997 年度実績報告書

自己・非自己識別システムの構造・機能・起源

研究課題

研究課題/領域番号	09044247
研究機関	北海道大学
研究代表者	笠原正典北海道大学, 医学部, 助教授 (30241318)
研究分担者	KAUFMAN Jame Institute for Animal Health(イギリス), 部長 DU Pasquier バーゼル免疫学研究所(スイス), 永世研究員 FLAJNIK Mart メリーランド大学(米国), 教授
キーワード	進化 / 自己・非自己識別システム / 主要組織適合遺伝子複合体 / 染色体重複
研究概要	ヒトやマウスがもつ精巧な自己・非自己識別システムは,長い時間をかけて行われた試行錯誤の結果,形成されたものであり,言うまでもなく「進化」の所産である.したがって,システムの全貌を総合的に理解するためには,ヒトやマウスのみを研究の対象としていたのでは不十分である.そこで,本研究では,ヒトから魚におよぶ脊椎動物を研究の対象として,自己・非自己識別システムの構造,機能,由来を探ることを目的とした.研究代表者は,プロテアソーム遺伝子群を解析することにより,ヒトの9q33-q34領域,マウスの第2染色体傍動原体領域に主要組織適合遺伝子複合体(MHC)様の遺伝領域が存在することを明らかにした.この遺伝領域とMHC領域は抗原処理遺伝子(プロテアソームのbetaサブユニットをコードするLMP遺伝子とTAP遺伝子)の祖先遺伝子をまきこんだ染色体重複によって分岐・形成されたものと想定された.系統発生的な解析を行うことにより,この染色体重複は今から4億年以上も前に,有顎脊椎動物の共通祖先に起こったものであることが判明した.Flajnikは,ヒトやマウスではMHCクラスII遺伝子の近傍に存在する.LMP,TAP遺伝子がアフリカツメガエルではクラスI遺伝子の近傍に位置していることを明らかにした.これから,アフリカツメガエルでは本来のMHCのゲノム構造が良く温存されているものと考えられた.Du Pasquierはアフリカツメガエルの胸腺皮質リンパ球に特異的に発現される免疫グロブリン超遺伝子族分子CTXをコードする遺伝子がMHC内でコードされていることを示した.KaufmanはニワトリMHCの全体をコスミド・コンティグとしてク-ロニングし物理地図を作製した.

研究成果
(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Kasahara, M., Nakaya, J., Satta, Y.and Takahata, N.: "Chromosomal duplication and the emergence of the adaptive immune system" Trends Genet.13. 90-92 (1997)
[文献書誌] Seboun, E., Barbaux, S., Bourgeron, T., Nishi, S., Algonik, A., Egashira, M., Niikawa, N., Bishop, C., Fellous, M., McElreavey, K.and kasahara, M.: "Gene sequence, localization, and evolutionary conservation of DAZLA, a candidate male sterility gene" Genomics. 41. 227-235 (1997)
[文献書誌] Hayashi, M., Ishibashi, T., Tanaka, K.and Kasahara, M.: "The mouse genes encoding the third pair of β-type proteasome subunits regulated reciprocally by IFN-γ : Structural comparison, chromosomal localization, and analysis of the promoter" J.Immunol.159. 2760-2770 (1997)
[文献書誌] Kandil, E., Kohda, K., Ishibashi, T., Tanaka, K.and Kasahara, M.: "PA28 Subunits of the mouse proteasome : primary structures and chromosomal localization of the genes" Immunogenetics. 46. 337-344 (1997)
[文献書誌] Kasahara, M.: "New insights into the genomic organization and origin of the major histocompatibility complex : Role of chromosomal (genome) duplication in the emergence of the adaptive immune system" Hereditas. 127(specialissue). 59-65 (1997)
[文献書誌] Kohda, K., Matsuda, Y., Ishibashi, T., Tanaka, K. and Kasahara, M.: "Structural analysis and chromosomal localization of the mouse Psmb5 gene coding for the constitutively expressed β-type proteasome subunit" Immunogenetics. 47. 77-87 (1997)
[文献書誌] Nonaka, M., Namikawa-Yamada, C., Sasaki, M., Salter-Cid, L., Flajnik, M.F.: "Evolution of proteasome subunits delta and LMP2 : complementary DNA cloning and linkage analysis with MHC in lower vertebrates" J.Immunol.159・2. 734-740 (1997)
[文献書誌] Nonaka, M., Namikawa, C., Kato, Y., Sasaki, M., alter-Cid, L., Flajnik, M.F.: "Major histocompatibility complex gene mapping in the amphibian Xenopus implies a primordial organization" Proc.Natl.Acad.Sci.USA.94・11. 5789-5791 (1997)
[文献書誌] Mckinney, E.C., Flajnik, M.F.: "IgM-mediated opsonization and cytotoxicity in the shark" J.Leuk.Biol.61・2. 141-146 (1997)
[文献書誌] Hansen, J.D., Strassburger, P., Du Pasquier, L.: "Conservation of a master hematopoietic switch gene during vertebrate evolution : isolation and characterization of Ikaros from teleost and amphibian species" Eur.J.Immunol.27・11. 3049-3058 (1997)
[文献書誌] Mussmann, R., Courtet, M., Schwager, J., Du Pasquier, L.: "Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals" Eur.J.Immunol.27・10. 2610-2619 (1997)
[文献書誌] Lassegues, M., Milochau, A., Doignon, F., Du Pasquier, L., Valembois, P.: "Sequence and expression of an Eisenia-fetida-derived cDNA clone that encodes the 40-kDa fetidin antibacterial protein" Eur.J.Biochem.246・3. 756-762 (1997)
[文献書誌] Wilson, M., Bengten, E., Miller, N.W., Clem.L.W., Du Pasquier, L., Warr, G.W.: "A novel chimeric Ig heavy chain from a teleost fish shares similarities to IgD." Proc.Natl.Acad.Sci.USA.94・9. 4593-4597 (1997)
[文献書誌] Chretien, I., Marcuz, A., Fellah, J., Charlemagne, J., Du Pasquier, L.: "The T cell receptor beta genes of Xenopus" Eur.J.Immunol.27・3. 763-771 (1997)
[文献書誌] Robert, J., Chretien, I., Guiet, C., Du Pasquier, L.: "Cross-linking CTX, a novel thymocyte-specific molecule, inhibits the growth of lymphoid tumor cells in Xenopus" Mol.Immunol.34・2. 133-143 (1997)
[文献書誌] Robert, J., Guiet, C., Cohen, N., Du Pasquier, L.: "Effects of thymectomy and tolerance induction on tumor immunity in adult Xenopus laevis" Int.J.Cancer. 70・3. 330-334 (1997)
[文献書誌] Kohda, K., Ishibashi, T., Shimbara, N., Tanaka, K., Matsuda, Y.and kasahara, M.: "Characterization of the mouse PA28 activator complex gene family : complete organizations of the three member genes and a physical map of the 〜150-kb region containing the α- and β-subunit genes" J.Immunol.160(in press). (1998)
[文献書誌] Kirchhoff, C., Osterhoff, C., Kasahara, M.and Ivell, R.: "Molecular biology of sperm maturation -New strategies for male contraception? In : M.Rajalakshmi (ed.) : Male Contraception : Present and Future" World Health Organization, Geneva. (in press). (1998)
[文献書誌] Tanaka, K.and kasahara, M.: "The MHC class I ligand generating system : Roles of immunoproteasomes and the IFN-γ-inducible PA28 complex" Immunol. Rev.163(in press). (1998)
[文献書誌] kasahara, M.: "Origin of the adaptive immune system : insights from the study of the major histocompatibility complex" Immunol. Rev.166(in press). (1998)

1997 年度 実績報告書

自己・非自己識別システムの構造・機能・起源

研究代表者

笠原 正典 北海道大学, 医学部, 助教授 (30241318)

研究成果

[文献書誌] Kasahara, M., Nakaya, J., Satta, Y.and Takahata, N.: "Chromosomal duplication and the emergence of the adaptive immune system" Trends Genet.13. 90-92 (1997)

[文献書誌] Seboun, E., Barbaux, S., Bourgeron, T., Nishi, S., Algonik, A., Egashira, M., Niikawa, N., Bishop, C., Fellous, M., McElreavey, K.and kasahara, M.: "Gene sequence, localization, and evolutionary conservation of DAZLA, a candidate male sterility gene" Genomics. 41. 227-235 (1997)

[文献書誌] Hayashi, M., Ishibashi, T., Tanaka, K.and Kasahara, M.: "The mouse genes encoding the third pair of β-type proteasome subunits regulated reciprocally by IFN-γ : Structural comparison, chromosomal localization, and analysis of the promoter" J.Immunol.159. 2760-2770 (1997)

[文献書誌] Kandil, E., Kohda, K., Ishibashi, T., Tanaka, K.and Kasahara, M.: "PA28 Subunits of the mouse proteasome : primary structures and chromosomal localization of the genes" Immunogenetics. 46. 337-344 (1997)

[文献書誌] Kasahara, M.: "New insights into the genomic organization and origin of the major histocompatibility complex : Role of chromosomal (genome) duplication in the emergence of the adaptive immune system" Hereditas. 127(specialissue). 59-65 (1997)

[文献書誌] Kohda, K., Matsuda, Y., Ishibashi, T., Tanaka, K. and Kasahara, M.: "Structural analysis and chromosomal localization of the mouse Psmb5 gene coding for the constitutively expressed β-type proteasome subunit" Immunogenetics. 47. 77-87 (1997)

[文献書誌] Nonaka, M., Namikawa-Yamada, C., Sasaki, M., Salter-Cid, L., Flajnik, M.F.: "Evolution of proteasome subunits delta and LMP2 : complementary DNA cloning and linkage analysis with MHC in lower vertebrates" J.Immunol.159・2. 734-740 (1997)

[文献書誌] Nonaka, M., Namikawa, C., Kato, Y., Sasaki, M., alter-Cid, L., Flajnik, M.F.: "Major histocompatibility complex gene mapping in the amphibian Xenopus implies a primordial organization" Proc.Natl.Acad.Sci.USA.94・11. 5789-5791 (1997)

[文献書誌] Mckinney, E.C., Flajnik, M.F.: "IgM-mediated opsonization and cytotoxicity in the shark" J.Leuk.Biol.61・2. 141-146 (1997)

[文献書誌] Hansen, J.D., Strassburger, P., Du Pasquier, L.: "Conservation of a master hematopoietic switch gene during vertebrate evolution : isolation and characterization of Ikaros from teleost and amphibian species" Eur.J.Immunol.27・11. 3049-3058 (1997)

[文献書誌] Mussmann, R., Courtet, M., Schwager, J., Du Pasquier, L.: "Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals" Eur.J.Immunol.27・10. 2610-2619 (1997)

[文献書誌] Lassegues, M., Milochau, A., Doignon, F., Du Pasquier, L., Valembois, P.: "Sequence and expression of an Eisenia-fetida-derived cDNA clone that encodes the 40-kDa fetidin antibacterial protein" Eur.J.Biochem.246・3. 756-762 (1997)

[文献書誌] Wilson, M., Bengten, E., Miller, N.W., Clem.L.W., Du Pasquier, L., Warr, G.W.: "A novel chimeric Ig heavy chain from a teleost fish shares similarities to IgD." Proc.Natl.Acad.Sci.USA.94・9. 4593-4597 (1997)

[文献書誌] Chretien, I., Marcuz, A., Fellah, J., Charlemagne, J., Du Pasquier, L.: "The T cell receptor beta genes of Xenopus" Eur.J.Immunol.27・3. 763-771 (1997)

[文献書誌] Robert, J., Chretien, I., Guiet, C., Du Pasquier, L.: "Cross-linking CTX, a novel thymocyte-specific molecule, inhibits the growth of lymphoid tumor cells in Xenopus" Mol.Immunol.34・2. 133-143 (1997)

[文献書誌] Robert, J., Guiet, C., Cohen, N., Du Pasquier, L.: "Effects of thymectomy and tolerance induction on tumor immunity in adult Xenopus laevis" Int.J.Cancer. 70・3. 330-334 (1997)

[文献書誌] Kirchhoff, C., Osterhoff, C., Kasahara, M.and Ivell, R.: "Molecular biology of sperm maturation -New strategies for male contraception? In : M.Rajalakshmi (ed.) : Male Contraception : Present and Future" World Health Organization, Geneva. (in press). (1998)

[文献書誌] Tanaka, K.and kasahara, M.: "The MHC class I ligand generating system : Roles of immunoproteasomes and the IFN-γ-inducible PA28 complex" Immunol. Rev.163(in press). (1998)

[文献書誌] kasahara, M.: "Origin of the adaptive immune system : insights from the study of the major histocompatibility complex" Immunol. Rev.166(in press). (1998)

1997 年度実績報告書

笠原正典北海道大学, 医学部, 助教授 (30241318)