1999 Fiscal Year Annual Research Report

自己・非自己識別システムの起源と進化:ゲノム重複の適応免疫系誕生における役割

Research Project

Project/Area Number	10044223
Research Category	Grant-in-Aid for Scientific Research (B)
Research Institution	The Graduate University for Advanced Studies
Principal Investigator	笠原正典総合研究大学院大学, 先導科学研究科, 教授 (30241318)
Keywords	ゲノム重複 / MHC / NAR / CTX
Research Abstract	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,主要組織適合遺伝子複合体(MHC)領域が大規模な染色体重複によって形成されたものであることをあきらかにした.MHC領域をまきこんだ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と想定され,ゲノム重複の一環として起こった可能性か強く示唆された.分担者の一人であるFlajnikはアフリカツメガエルMHCのゲノム構造の解析を推進するとともに,軟骨魚類で同定されたNAR遺伝子の多様性形成機構に関し新知見を得た.Du Pasquierは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CTXに関する研究を精力的に推進し,本超遺伝子族に属する多数の新規遺伝子をヒトにおいて同定した.また,同じく分担者の一人であるKaufmanはニワトリMHCの全塩基配列を決定し,ニワトリのMHCにはプロテアソーム遺伝子が存在しないこと,NK receptor様のC-typeレクチン遺伝子が存在することなど,多くの興味深い知見を得た.

Research Products
(14 results)

All Other

All Publications (14 results)

[Publications] 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. 4923-4935 (1998)
[Publications] Tanaka K.and Kasahara M.: "The MHC class I ligand generating system: Roles of immunoproteasomes and the interferon-γ-inducible proteasome activator PA28"Immunol. Rev.. 163. 161-176 (1998)
[Publications] Suto Y.,Ishikawa Y.,Kasahara M.,Kasai F.,Yabe T.,Akaza T.and Juji T.: "Gene arrangement of the killer cell inhibitory receptor family on human chromosome 19q13.4 detected by fiber-FISH"Immunogenetics. 48. 235-241 (1998)
[Publications] Kasahara M.: "The chromosomal duplication model of the major histocompatibility complex"Immunol. Rev.. 167. 17-32 (1998)
[Publications] Kasahara M.: "What do the paralogous regions in the genome tell us about the origin of the adaptive immune system?"Immunol. Rev.. 166. 159-175 (1998)
[Publications] Nishi S.,Hoshi N.,Kasahara M.,Ishibashi T.and Fujimoto S.: "Existence of human DAZLA protein in the cytoplasm of human oocytes"Mol. Hum. Reprod.. 5. 495-497 (1999)
[Publications] Flajnik M.F.,Ohta Y.,Greenberg A.S.,Salter-Cid L.,Carrizosa A.,Du Pasquier L.and Kasahara M.: "Two ancient allelic lineages at the single classical class I locus in the Xenopus MHC"J. Immunol.. 163. 3826-3833 (1999)
[Publications] Kasahara M.: "Genome dynamics of the major histocompatibility complex: insights from genome paralogy"Immunogenetics. 50. 134-145 (1999)
[Publications] Murata S.,Kawahara H.,Tohma S.,Yamamoto K.,Kasahara M.,Nabeshima Yi.,Tanaka K.and Chiba T.: "Growth retardation in mice lacking the proteasome activator PA28γ"J. Biol. Chem.. 274. 38211-38215 (1999)
[Publications] Kirchhoff C.,Osterhoff C.,Kasahara M.and Ivell R.: "Molecular biology of sperm maturation - New strategies for male contraception?"Male Contraception: Present and Future. 103-123 (1999)
[Publications] Kasahara M.and Tanaka K.: "Proteasomes and antigen presentation: biochemistry and genetics"Recent Res. Dev. Immunol.. 1. 印刷中 (2000)
[Publications] Kasahara M.,Yawata M.and Suzuki T.: "The MHC paralogous group: Listing of members and a brief overview"Major Histocompatibility Complex: Evolution, Structure, and Function. 27-44 (2000)
[Publications] Kasahara M.: "Genome paralogy: A new perspective on the organization and origin of the major histocompatibility complex"Curr. Top. Microbiol. Immunol.. 248. 53-66 (2000)
[Publications] Kasahara M.(ed.): "Major Histocompatibility Complex: Evolution, Structure, and Function"Springer-Verlag, Tokyo-Berlin-Heidelberg-New York. 561 (2000)

1999 Fiscal Year Annual Research Report

自己・非自己識別システムの起源と進化:ゲノム重複の適応免疫系誕生における役割

Principal Investigator

笠原 正典 総合研究大学院大学, 先導科学研究科, 教授 (30241318)

Research Products

[Publications] Tanaka K.and Kasahara M.: "The MHC class I ligand generating system: Roles of immunoproteasomes and the interferon-γ-inducible proteasome activator PA28"Immunol. Rev.. 163. 161-176 (1998)

[Publications] Suto Y.,Ishikawa Y.,Kasahara M.,Kasai F.,Yabe T.,Akaza T.and Juji T.: "Gene arrangement of the killer cell inhibitory receptor family on human chromosome 19q13.4 detected by fiber-FISH"Immunogenetics. 48. 235-241 (1998)

[Publications] Kasahara M.: "The chromosomal duplication model of the major histocompatibility complex"Immunol. Rev.. 167. 17-32 (1998)

[Publications] Kasahara M.: "What do the paralogous regions in the genome tell us about the origin of the adaptive immune system?"Immunol. Rev.. 166. 159-175 (1998)

[Publications] Nishi S.,Hoshi N.,Kasahara M.,Ishibashi T.and Fujimoto S.: "Existence of human DAZLA protein in the cytoplasm of human oocytes"Mol. Hum. Reprod.. 5. 495-497 (1999)

[Publications] Flajnik M.F.,Ohta Y.,Greenberg A.S.,Salter-Cid L.,Carrizosa A.,Du Pasquier L.and Kasahara M.: "Two ancient allelic lineages at the single classical class I locus in the Xenopus MHC"J. Immunol.. 163. 3826-3833 (1999)

[Publications] Kasahara M.: "Genome dynamics of the major histocompatibility complex: insights from genome paralogy"Immunogenetics. 50. 134-145 (1999)

[Publications] Murata S.,Kawahara H.,Tohma S.,Yamamoto K.,Kasahara M.,Nabeshima Yi.,Tanaka K.and Chiba T.: "Growth retardation in mice lacking the proteasome activator PA28γ"J. Biol. Chem.. 274. 38211-38215 (1999)

[Publications] Kirchhoff C.,Osterhoff C.,Kasahara M.and Ivell R.: "Molecular biology of sperm maturation - New strategies for male contraception?"Male Contraception: Present and Future. 103-123 (1999)

[Publications] Kasahara M.and Tanaka K.: "Proteasomes and antigen presentation: biochemistry and genetics"Recent Res. Dev. Immunol.. 1. 印刷中 (2000)

[Publications] Kasahara M.,Yawata M.and Suzuki T.: "The MHC paralogous group: Listing of members and a brief overview"Major Histocompatibility Complex: Evolution, Structure, and Function. 27-44 (2000)

[Publications] Kasahara M.: "Genome paralogy: A new perspective on the organization and origin of the major histocompatibility complex"Curr. Top. Microbiol. Immunol.. 248. 53-66 (2000)

[Publications] Kasahara M.(ed.): "Major Histocompatibility Complex: Evolution, Structure, and Function"Springer-Verlag, Tokyo-Berlin-Heidelberg-New York. 561 (2000)

笠原正典総合研究大学院大学, 先導科学研究科, 教授 (30241318)