MHCクラスIb分子の構造と機能

• 研究課題/領域番号: 07670359
• 研究種目: 基盤研究(C)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 免疫学
• 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)
• 研究期間 (年度): 1995 – 1996
• 研究課題ステータス: 完了 (1996年度)
• 配分額: 600千円 (直接経費: 600千円); 1996年度: 600千円 (直接経費: 600千円)
• キーワード: 主要組織適合遺伝子複合体 / クラスIb分子 / FcRn遺伝子 / 染色体重複 / Fcリセプター

研究概要

主要組織適合遺伝子複合体(MHC)クラスI分子には,抗原提示に主役を演じるクラスIa分子の他に,クラスIb分子と総称される多様な分子群が存在する(Transplant Immunol.3:1,1995;Res.Immunol.147:278,1996).IgGを胎盤・腸管において輸送するFcRn分子,糖脂質を抗原提示するCD1分子,機能不明のZn-α2 糖タンパク質分子,ヘマクロマトーシスの病因分子と想定されるHLA-H分子などが代表的なクラスIb分子である.本研究では,前三者のクラスIb分子を対象として,以下の成果を得た.
1)マウスおよびヒトのFcRn分子をコードする遺伝子をクローニングし,その構造・染色体局在を決定した(J.Immunol.154:5907,1995;Cytogenet.Cell Genet.73:97,1996).
2)ヒトCD1遺伝子の存在する領域とMHC領域が染色体重複によって形成されたことを明らかにした(Proc.Natl.Acad.Sci.USA 93:9096,1996;Trends in Genetics 13:in press,1997).
3)マウスのZn-α2 糖タンパク質分子がMHC領域外でコードされていることを示した(Immunogenetics 42:72,1995).
4)ヒトのCD1b分子を胸腺から精製し,CD1b分子に結合する内在性ペプチドの有無を検索した.その結果,CD1b分子にはペプチドは結合していない可能性が高いことが判明した.

研究成果

• [文献書誌] Kandil, E.: "Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene." J. Immunol.154. 5907-5918 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kasahara, M.: "Mapping of acidic epididymal glycoprotein (Aeg) genes to mouse chromosome 17." Mammalian Genome. 6. 52-54 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kasahara, M.: "Evolution of the major histocompatibility complex : A current overview." Transplant Immunol.3. 1-20 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Noguchi, M.: "The MHC class I-like Zn-α2-glycoprotein gene maps to mouse chromosome 5." Immunogenetics. 42. 72-74 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kobari, F.: "Exon-intron organization of Xenopus MHC class II β-chain genes." Immunogenetics. 42. 376-385 (1995)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kasahara, M.: "Chromosomal localization of the mouse proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex." Proc. Natl. Acad. Sci. U. S. A.93. 9096-9101 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kandil, E.: "Isolation of low molecular mass polypeptide complementary DNA clones from primitive vertebrates : Implications for the origin of MHC class I-restricted antigen presentation." J. Immunol.156. 4245-4253 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hayashi, M.: "Characterization of a human glycoprotein with a potential role in sperm-egg fusion : cDNA cloning, immunohistochemical localization, and chromosomal assignment of the gene (AEGL1)." Genomics. 32. 367-374 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kandil, E.: "The human gene encoding the heavy chain of the major histocompatibility complex class I-like Fc receptor (FCGRT) maps to 19q13. 3." Cytogenet. Cell Genet.73. 97-98 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kasahara, M.: "Origin and evolution of the class I gene family : Why are some of the mammalian class I genes encoded outside the major histocompatibility complex?" Res. Immunol.147. 278-284 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kasahara, M.: "Origin and evolution of the class I gene family : Why are some of the mammalian class I genes encoded outside the major histocompatibility complex? Rebuttal to the commentary by Drs. Ahouse and Simister." Res. Immunol.147. 353 (1996)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Hayashi, 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.(in press). (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Seboun, E.: "Gene sequence, localization and evolutionary conservation of DAZLA, a candidate male sterility gene." Genomics. 42(in press). (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kirchhoff, C.: "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). (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kasahara, M.: "Chromosomal duplication and the emergence of the adaptive immune system." Trends Genet.13(in press). (1997)
  • 説明: 「研究成果報告書概要(和文)」より
• [文献書誌] Kandil, E.: "Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene." J.Immunol.154. 5907-5918 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kasahara, M.: "Mapping of acidic epididymal glycoprotein (Aeg) genes to mouse chromosome 17." Mammalian Genome. 6. 52-54 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kasahara, M.: "Evolution of the major histocompatibility complex : A current overview." Transplant Immunol.3. 1-20 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Noguchi, M.: "The MHC class I-like Zn-alpha2-glycoprotein gene maps to mouse chromosome 5." Immunogenetics. 42. 72-74 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kobari, F.: "Exon-intron organization of Xenopus MHC class II beta-chain genes." Immunogenetics. 42. 376-385 (1995)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kasahara, M.: "Chromosomal localization of the mouse proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex." Proc.Natl.Acad.Sci.U.S.A. 93. 9096-9101 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kandil, E.: "Isolation of low molecular mass polypeptide complementary DNA clones from primitive vertebrates : Implications for the origin of MHC class I-restricted antigen presentation." J.Immunol.156. 4245-4253 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hayashi, M.: "Characterization of a human glycoprotein with a potential role in sperm-egg fusion : cDNA cloning, immunohistochemical localization, and chromosomal assignment of the gene (AEGL1)." Genomics. 32. 367-374 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kandil, E.: "The human gene encoding the heavy chain of the major histocompatibility complex class I-like Fc receptor (FCGRT) maps to 19q13.3." Cytogenet.Cell Genet. 73. 97-98 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kasahara, M.: "Origin and evolution of the class I gene family : Why are some of the mammalian class I genes encoded outside the major histocompatibility complex?" Res.Immunol.147. 278-284 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kasahara, M.: "Origin and evolution of the class I gene family : Why are some of the mammalian class I genes encoded outside the major histocompatibility complex? Rebuttal to the commentary by Drs.Ahouse and Simister." Res.Immunol.147. 353 (1996)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Hayashi, M.: "The mouse genes encoding the third pair of beta-type proteasome subunits regulated reciprocally by IFN-gamma : Structural comparison, chromosomal localization, and analysis of the promoter." J.Immunol. (in press).
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Seboun, E.: "Gene sequence, localization and evolutionary conservation of DAZLA,a candidate male sterility gene." Genomics. 42 (in press). (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kirchhoff, C.: "Molecular biology of sperm maturation : New strategies for male contraception?" In : M.Rajalakshmi (ed.) : Male Contraception : Present and Future, in press, World Health Organization, Geneva. (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kasahara, M.: "Chromosomal duplication and the emergence of the adaptive immune system." Trends Genet.13 (in press). (1997)
  • 説明: 「研究成果報告書概要(欧文)」より
• [文献書誌] Kandil, E.: "Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene." J. Immunol.154. 5907-5918 (1995)
• [文献書誌] Kasahara, M.: "Mapping of acidic epididymal glycoprotein (Aeg) genes to mouse chromosome 17." Mammalian Genome. 6. 52-54 (1995)
• [文献書誌] Kasahara, M.: "Evolution of the major histocompatibility complex : A current overview." Transplant Immunol.3. 1-20 (1995)
• [文献書誌] Noguchi, M.: "The MHC class I-like Zn-α2-glycoprotein gene maps to mouse chromosome 5." Immunogenetics. 42. 72-74 (1995)
• [文献書誌] Kobari, F.: "Exon-intron organization of Xenopus MHC class II β-chain genes." Immunogenetics. 42. 376-385 (1995)
• [文献書誌] 笠原正典: "MHCはどのように進化してきたのか? 非哺乳類MHC遺伝子の解析からわかったこと." 日本組織適合性学会誌. 1. 135-138 (1995)
• [文献書誌] 笠原正典: "主要組織適合遺伝子複合体分子のペプチド結合ドメインの起源.菊地浩吉,矢田純一,奥村 康 編集" Annual Review免疫1995,中外医学社,東京. 164-170 (1995)
• [文献書誌] 笠原正典: "ストレスタンパク質70とMHC." 生体の科学. 46. 303-307 (1995)
• [文献書誌] 笠原正典: "MHCの進化からみた免疫学." 日本免疫学会会報. 3(No.2). 7-8 (1995)
• [文献書誌] 笠原正典: "MHCクラスI分子による抗原提示システム." 免疫 Immunology Frontier. 5. 465-477 (1995)
• [文献書誌] 牛木辰男: "原子間力顕微鏡(AFM)-その原理と医生物応用." 細胞. 27. 538-542 (1995)
• [文献書誌] Kasahara, M.: "Chromosomal localization of the mouse proteasome Z subunit gene reveals an ancient chromosomal duplication involving the major histocompatibility complex." Proc. Natl. Acad. Sci. U.S.A.93. 9096-9101 (1996)
• [文献書誌] Kandil, E.: "Isolation of low molecular mass polypeptide complementary DNA clones from primitive vertebrates : Implications for the origin of MHC class I-restricted antigen presentation." J. Immunol.156. 4245-4253 (1996)
• [文献書誌] Hayashi, M.: "Characterization of a human glycoprotein with a potential role in sperm-egg fusion : cDNA cloning, immunohistochemical localization, and chromosomal assignment of the gene (AEGL1)." Genomics. 32. 367-374 (1996)
• [文献書誌] Kandil, E.: "The human gene encoding the heavy chain of the major histocompatibility complex class I-like Fc receptor (FCGRT) maps to 19q 13.3." Cytogenet. Cell Genet.73. 97-98 (1996)
• [文献書誌] Kasahara, M.: "Origin and evolution of the class I gene family : Why are some of the mammalian class I genes encoded outside the major histocompatibility complex?" Res. Immunol.147. 278-284 (1996)
• [文献書誌] Kasahara, M.: "Origin and evolution of the class I gene family : Why are some of the mammalian class I genes encoded outside the major histocompatibility complex? Rebuttal to the commentary by Drs. Ahouse and Simister." Res. Immunol.147. 353 (1996)
• [文献書誌] 笠原正典: "MHC分子の表出にかかわるシャペロン." 臨床免疫. 28. 291-297 (1996)
• [文献書誌] 笠原正典: "主要組織適合遺伝子複合体領域をまきこんだ太古の染色体重複." 生化学. 68. 1717-1721 (1996)
• [文献書誌] 笠原正典: "主要組織適合遺伝子複合体領域は脊椎動物ゲノムにおいて重複している." 臨床免疫. 29. 259-264 (1997)
• [文献書誌] Hayashi, 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.(in press). (1997)
• [文献書誌] Seboun, E.: "Gene sequence, localization and evolutionary conservation of DAZLA, a candidate male sterility gene." Genomics. 42(in press). (1997)
• [文献書誌] Kirchhoff, C.: "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). (1997)
• [文献書誌] Kasahara, M.: "Chromosomal duplication and the emergence of the adaptive immune system." Trends Genet.13(in press). (1997)
• [文献書誌] 笠原正典: 脊椎動物進化の初期に起こった免疫系のビッグバン.高畑尚之 編集:生命システムの歴史性.(印刷中), (1997)
• [文献書誌] Kasahara,M.,Flajnik,M.F.,Ishibashi,T.and Natori,T.: "Evolution of the major histocompatibility complex: A current overview." Transplant Immunol.3. 1-20 (1995)
• [文献書誌] Kasahara,M.,Hayashi,M.,Yoshida,M.C.,Nadeau,J.H.,Fujimoto,S.and Isibashi,T.: "Mapping of acidic epididymal glycoprotein(Aeg)genes to mouse chromosome 17." Mammalian Genome. 6. 52-54 (1995)
• [文献書誌] Noguchi,M.,Kitabatake,A.,Ishibashi,T.and Kasahara,M.: "The MHC class I-like Zn-a2-glycoprotein gene maps to mouse chromosome 5." Immunogenetics. 42. 72-74 (1995)
• [文献書誌] Kandil,E.,Noguchi,M.,Ishibashi,T.and Kasahara,M.: "Structural and phylogenetic analysis of the MHC class I-like Fc receptor gene." J.Immunol.154. 5907-5918 (1995)
• [文献書誌] Kobari,F.,Sato,K.,Shum,B.P.,Tochinai,S.,Katagiri,M.,Ishibashi,T.,Du Paxquier,L.,Flajnik,M.F.and Kasahara,M.: "Exon-intron organization of Xenopus MHC class II β-chain genes." Immunogenetics. 42. 376-385 (1995)
• [文献書誌] Hayashi,M.,Fujimoto,S.,Takano,H.,Ushiki,T.,Abe,K.,Isikura,H.,and Yoshida.M.C.,Kirchhoff,C.,Ishibashi,T. and Kasahara,M.: "Characterization of a human glycoprotein with a potential role in spermegg fusion: cDNA cloning,immunohistochemical localization,chromosomal assignment of the gene." Genomics. 33(in press). (1996)
• [文献書誌] Kandil,E.,Egashira,M.,Miyosi,O.,Ishibashi,T.,Niikawa,N.and Kasahara,M.: "The human gene encoding the major histocompatibility complex class I-like Fc receptor(FCGRT)maps to 19q13.3." Cytogenet.Cell Genet.72(in press). (1996)
• [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,in press.Wiley.(in press). (1996)
• [文献書誌] Kandil,E.,Namikawa,C.,Nonaka,M.,Greenberg,A.S.,Flajnik,M.F.,Ishibashi,T.and Kasahara,M.: "Isolation of low molecular mass polypeptide cDNA clones from primitive vertebrates:Implications for the origin of MHC class I- restricted antigen presentation." J.Immunol.(in press). (1996)
• [文献書誌] Flajnik,M.F.,Salter-Cid,L.,Kandil,E.and Kasahara,M.: "Evolution of the major histocompatibility complex class Ib genes." Res.Immunol.(in press). (1966)