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The Self-Nonself Discrimination System of Vertebrates : Structure, Function, and Origin

Research Project

Project/Area Number 09044247
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Immunology
Research InstitutionHokkaido University

Principal Investigator

KASAHARA Masanori  Hokkaido University School of Medicine, Department of Biochemistry, Associate Professor, 医学部, 助教授 (30241318)

Co-Investigator(Kenkyū-buntansha) KAUFMAN James  Institute for Animal Helth, Head, 部長
PASQUIER Louis Du  Basel Institute for Immunology, Pearmanent Member, 永世研究員
FLAJNIK Martin  University of Maryland School of Medicine, Department of Microbiology and Immuno, 教授
DU Pasquier  バーゼル免疫学研究所(スイス), 永世研究員
Project Period (FY) 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1997: ¥3,800,000 (Direct Cost: ¥3,800,000)
KeywordsMajor histocompatibility complex / Evolution / Self-nonself discrimination system / Chromosome duplication
Research Abstract

The exquisite self-nonself discrimination system, as we see now in man and mouse, was built over evolutionary time. Therefore, to truly understand the biological significance of the system, it is insufficient to study only humans and mice. The aim of the present work was, thus, to study the structure, function, and origin of the vertebrate self-nonself discrimination system employing a wide variety of animals ranging from mammals to fish. The head investigator found that the genome of mammals such as humans and mice contains the regions paralogous to the major histocompatibility complex (MHC). These regions and the MHC region appear to have diverged as a result of chromosomal duplication involving the ancestors of the antigen processing genes such as LMP (low molecular mass polypeptide) and TAP (transporter associated with antigen processing). Phylogenetic analysis showed that the chromosomal duplications probably took place early in vertebrate evolution, in a common ancestor of jawed vertebrates. Dr.Flajnik found that the LMP and TAP genes are located more closely to MHC class I than to class II genes in the amphibian Xenopus laevis. This is in contrast to the fact that these genes reside in the class II region of the mammalian MHC,and suggests that the Xenopus type gene organization is a primordial one. Dr.Du Pasquier found that the Xenopus CIX gene coding for the Ig superfamily member expressed specifically in cortical thymocytes is linked to the MHC.Dr.Kaufman established a cosmid contig map covering the entire chicken MHC.

Report

(2 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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:Structual comparison, chromosomal localization, and analysis of the promoter." J.Immunol.159. 2760-2770 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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(special issue). 59-65 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nonaka,M., Namikawa,C., Kato,Y., Sasaki,M., Salter-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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] McKinney,E.C.,flajnik,M.F.: "IgM-mediated opsonization and cytotoxicity in the shark." J.Leuk.Biol.61・2. 141-146 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mussmann,R.,Courtet,M.,Schwager,J.,Du Pasquier,L.: "Microsites for immunoglobulin switch recombination breadpoints from Xenopus to mammals." Eur.J.Immunol.27・10. 2610-2619 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kasahara,M.: "Origin of the adaptive immune system: insights from the study of the major histocompatibility complex." Immunol. Rev.166(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hayashi, M., Ishibashi, T., Tanaka, K.and Kasahara, 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.159. 2760-2770 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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 (special issue). 59-65 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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 beta-type proteasome subunit." Immunogenetics. 47. 77-87 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nonaka, M., Namikawa-Yamada, C., Sasaki, M., Salter-Cid, L.and Flajnik, M.F.: "Evolution of proteasome subunits delta and LMP2 : complementary DNA cloning and linkage analysis with MHC in lower vertebrates" J.Immunol.159. 734-740 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nonaka, M., Namikawa, C., Kato, Y., Sasaki, M., Salter-Cid, L.and Flajnik, M.F.: "Major histocompatibility complex gene mapping in the amphibian Xenopus implies a primordial organization." Proc.Natl.Acad.Sci.USA. 94. 5789-5791 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] McKinney, E.C.and Flajnik, M.F.: "IgM-mediated opsonization and cytotoxicity in the shark." J.Leukoc.Biol.61. 141-146 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Hansen, J.D., Strassburger, P.and 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. 3049-3058 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mussmann, R., Courtet, M., Schwager, J.and Du Pasquier, L.: "Microsites for immunoglobulin switch recombination breakpoints from Xenopus to mammals." Eur.J.Immunol.27. 2610-2619 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Lassegues, M., Milochau, A., Doignon, F., Du Pasquier, L.and Valembois, P.: "Sequence and expression of an Eisenia-fetida-derived cDNA clone that encodes the 40-kDa fetidin antibacterial protein" Eur.J.Biochem.246. 756-762 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wilson, M., Bengten, E., Miller, N.W., Clem, L.W., Du Pasquier, L.and Warr, GW.: "A novel chimeric Ig heavy chain from a teleost fish shares similarities to IgD." Proc.Natl.Acad.Sci.USA. 94. 4593-4597 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Chretien, I., Marcuz, A., Fellah, J., Charlemagne, J.and Du Pasquier, L.: "The T cell receptor beta genes of Xenopus." Eur.J.Immunol.27. 763-771 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Robert, J., Chretien, I., Guiet, C.and Du Pasquier, L.: "Crosslinking CTX,a novel thymocyte-specific molecule, inhibits the growth of lymphoid tumor cells in Xenopus." Mol.Immunol.34. 133-143 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Robert, J., Guiet, C., Cohen, N.and Du Pasquier, L.: "Effects of thymectomy and tolerance induction on tumor immunity in adult Xenopus laevis." Int.J.Cancer.70. 330-334 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [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 alpha-and beta-subunit genes." J.Immunol.160, (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tanaka, K., Shimbara, N.and Kasahara, M.: "The MHC class I ligand generating system : Roles of immunoproteasomes and the IFN-gamma-inducible PA28 complex." Immunol.Rev.163, (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kasahara, M.: "Origin of the adaptive immune system : insights from the study of the major histocompatibility complex." Immunol.Rev.166, (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mckinney, E.C., Flajnik, M.F.: "IgM-mediated opsonization and cytotoxicity in the shark" J.Leuk.Biol.61・2. 141-146 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [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(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] 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)

    • Related Report
      1997 Annual Research Report
  • [Publications] kasahara, M.: "Origin of the adaptive immune system : insights from the study of the major histocompatibility complex" Immunol. Rev.166(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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