1994 Fiscal Year Annual Research Report

自己・非自己識別分子MHCの起源と進化

Research Project

Project/Area Number	05304003
Research Institution	The Graduate University for Advanced Studies
Principal Investigator	高畑尚之総合研究大学院大学, 教育研究交流センター, 教授 (30124217)
Co-Investigator(Kenkyū-buntansha)	堀寛名古屋大学, 理学部, 教授 (60116663) 池村淑道国立遺伝学研究所, 集団遺伝研究系, 教授 (50025475) 笠原正典北海道大学, 医学部, 助教授 (30241318) 小幡裕一愛知県がんセンター, 免疫学部, 室長 (30177290) 笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
Keywords	クローニング / 下等脊椎動物MHC / 非古典的MHC / HLA / 自己免疫 / MHC拘束 / 起源と進化 / T細胞レパートリー
Research Abstract	自己・非自己識別分子MHCの起源は、脊椎動物の出現時期とほぼ同一であることが明らかになった。橋本や笠原は、世界に先駆けて軟骨魚類のMHCの単離に成功し、その多様性のあり方が基本的には哺乳類のものと同じであることを示した。堀は魚類におけるMHCの遺伝子構成に注目し、3種のクラスII遺伝子群の存在を確認した。しかし、より下等な無鰐類からMHC遺伝子を単離する試みはすべて失敗に終わっていて、その他の知見と合わせMHC分子の出現が無鰐類の出現以降であったことが示唆された。以上は脊椎動物免疫系の起源が5億程前のカンブリア紀であり、このときMHCの他に免疫グロブリンやT細胞受容体分子なども同時に進化したことを示している。自己・非自己識別に重要な役割を担っている分子は古典的MHCであるが、機能が不明確な非古典的MHCも多数存在する。小幡、森脇と高畑はマウスの非古典的MHCであるTLに注目し、腸で強く発現することの生物的意義が特種な寄生体への対応であるという仮説をたてた。これを検証するためにTL特異的に結合するペプチドの単離を急いでいる。これは中枢免疫と局所免疫の関係など新しい問題を含んでいる。ヒトMHC(HLA)領域の遺伝的多様性と様々な疾患を明らかにするため、猪子、池村と笹月は4Mb領域の遺伝解析を進め、遺伝子密度、GC量、組換えホットスポット、DNAの複製点などの同定を行った。このことから疾患がおこる分子機構や脊椎動物のゲノム進化の道筋を解明する手がかりを得た。以上の成果は、世界的にみても第一級のものである。また班員間の研究協力も十分に進み添付リストにあるように班員の共著論文が多数発表された。

Research Products

(31 results)

All Other

All Publications (31 results)

[Publications] Takahata,N.: "Comments on the detection of reciprocal recombination or gene conversion." Immunogenetics. 39. 146-149 (1994)
[Publications] Satta,Y.: "Intensity of matural selection at the major histocompatibility complex loci." Proc.Natl.Acad.Sci.USA. 91. 7184-7188 (1994)
[Publications] Takahata,N.: "Divergence time and population size in the lineage leading to modern humans." Theor.Popul.Biol.(in press). (1995)
[Publications] Takahata,N.: "MHC diversity and selection." Immunological Review. (in press). (1995)
[Publications] Sugaya,K.: "Three genes in the human MHC class III region near the junction with the class II:gene for receptor of advanced glycosylation end products,PBX2 homeobox gene and a Norcth homolong,human counterpart of mouse mammary tumor gene int-3." Genomics. 23. 408-419 (1994)
[Publications] Matsumoto,K.: "The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C." J.Cell.Biol.125. 483-493 (1994)
[Publications] Ando,A.: "Cloning of a new kinesin‐related gene located at the centromeric end of the human MHC region." Immunogenetics. 39. 194-200 (1994)
[Publications] Yoshino,M.: "Recombination in the class III region of the mouse major histocompatibility complex." Immunogenetics. 40. 280-286 (1994)
[Publications] Morita,A.: "TL‐antigen as a transplantation antigen recognized by TL-restricted cytotoxic T cells." J.Exp.Med.179. 777-784 (1994)
[Publications] Obata,Y.: "The structure,function and evolution of mouse TL genes,nonclassical class I genes of the major histocompatibility complex." Proc,Natl.Acad.Sci.,USA. 91. 6589-6593 (1994)
[Publications] Obata,Y.: "TL genes in Asian wild mice.The evolutionary conserved nonclasical class I genes of the major histocompatibility complex.in Genetics in wild mice:its application to biomedical research." Japan Scientific Societies Press,Tokyo/S.Karger AG basel. 159-177 (1994)
[Publications] 小幡裕一: "生体防御における非古典的MHCクラスI分子の機能" 蛋白質・核酸・酵素臨時増刊号「エボリューション」. 39. 2626-2637 (1994)
[Publications] 堀寛: "自己-非自己識別機構の進化「生命体システムのなりたち」(小関治男、岡田節人編)" 講談社サイエンティフィック. 73-89 (1994)
[Publications] Salter-Cid,L.: "Hsp70 genes are kinked to the Xenopus major histocompatibility complex." Immunogenetics. 39. 1-7 (1994)
[Publications] Kasahara,M.: "Evolution of the major histocompatibility complex:A current overview." Transplant Immunol.2(in press). (1994)
[Publications] Kato,S.: "Isolation of the Xenopus complement factor B complementary DNA and linkage of the gene to the frog MHC." J.Immunol.153. 4546-4554 (1994)
[Publications] Kasahara,M.: "Mapping of acidic epididymal glycoprotein (Aeg) genes to mouse chromosome 17." Mammalian Genome. 5(in press). (1994)
[Publications] 笠原正典: "MHC遺伝子の起源と進化" 蛋白質・核酸・酵素. 39. 2606-2618 (1994)
[Publications] Haas,J.P.: "Polymorphism in the upstream regulatory regions of DQA1 genes and DRB1, QAP1,DQA1,DQB1 haplotypes in the German population." Hum.Immunol.39. 31-40 (1994)
[Publications] Koshizaka,T.: "A new HLA-DPB1 allele,DPB1^*SUT(DPB1^*4701)." Tissue Antigens.43. 50-53 (1994)
[Publications] Inoko,H.: "Role of human leukocyte antigens and T lymphocytes and in the immune response." Annals of Cancer Research and Therapy. 2. 173-191 (1994)
[Publications] Ogawa,K.: "A novel HLA-DPB1 allele,DPB1^*3601(DPB1^*KT)." Tissue Antigens. 44. 134-136 (1994)
[Publications] Sugaya,K.: "Three human MHC class III genes near the junction with the class II locus:gene for receptor of advanced glycosylation end products,HOX12 homeobox gene and a Notch-homolog,human counterpart of mouse mammary tumor gene int3." Genomics. 23. 408-419 (1994)
[Publications] Yoshino,M.: "No dose effect of recombinational hotspots in the mouse MHC." Immunogenetics. 39. 381-389 (1994)
[Publications] Yoshino,M.: "Recombination in the class III region of the mouse major histocompatibility complex." Immunogenetics. 40. 280-286 (1994)
[Publications] Hayasizaki,Y.: "Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method" Nature Genetics. 6. 33-40 (1994)
[Publications] Fukuda,Y.: "Negative effect of HLA-DQ antigen compatibility (Concordance on the survival of kidney grafts.)" Transplantation Proceedings. 26. 1887-1890 (1994)
[Publications] Yamamoto,K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA)class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice." J.Exp.Med.180. 165-171 (1994)
[Publications] Satoh,M.: "Genetic and immunological digfferences between Japanese patients with diffuse scleroderma and limited scleroderma." The Journal of Rheumatology. 21. 111-114 (1994)
[Publications] Takahata,N.: "Polymorphism at MHC loci and isolation by the immune system in vertebrates." (ed.B.Golding)in Non-neutral Evolution:Theories and Molecular Data(Chapman & Hall), 20 (1994)
[Publications] Moriwaki,K.: "Genetics in Wild mice." (eds.K.Moriwaki,T.Shiroishi,and H.Yonekawa)Japan Scientific Society Press, 333 (1994)

1994 Fiscal Year Annual Research Report

自己・非自己識別分子MHCの起源と進化

Principal Investigator

高畑尚之総合研究大学院大学, 教育研究交流センター, 教授 (30124217)

Research Products

[Publications] Takahata,N.: "Comments on the detection of reciprocal recombination or gene conversion." Immunogenetics. 39. 146-149 (1994)

[Publications] Satta,Y.: "Intensity of matural selection at the major histocompatibility complex loci." Proc.Natl.Acad.Sci.USA. 91. 7184-7188 (1994)

[Publications] Takahata,N.: "Divergence time and population size in the lineage leading to modern humans." Theor.Popul.Biol.(in press). (1995)

[Publications] Takahata,N.: "MHC diversity and selection." Immunological Review. (in press). (1995)

[Publications] Sugaya,K.: "Three genes in the human MHC class III region near the junction with the class II:gene for receptor of advanced glycosylation end products,PBX2 homeobox gene and a Norcth homolong,human counterpart of mouse mammary tumor gene int-3." Genomics. 23. 408-419 (1994)

[Publications] Matsumoto,K.: "The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C." J.Cell.Biol.125. 483-493 (1994)

[Publications] Ando,A.: "Cloning of a new kinesin‐related gene located at the centromeric end of the human MHC region." Immunogenetics. 39. 194-200 (1994)

[Publications] Yoshino,M.: "Recombination in the class III region of the mouse major histocompatibility complex." Immunogenetics. 40. 280-286 (1994)

[Publications] Morita,A.: "TL‐antigen as a transplantation antigen recognized by TL-restricted cytotoxic T cells." J.Exp.Med.179. 777-784 (1994)

[Publications] Obata,Y.: "The structure,function and evolution of mouse TL genes,nonclassical class I genes of the major histocompatibility complex." Proc,Natl.Acad.Sci.,USA. 91. 6589-6593 (1994)

[Publications] Obata,Y.: "TL genes in Asian wild mice.The evolutionary conserved nonclasical class I genes of the major histocompatibility complex.in Genetics in wild mice:its application to biomedical research." Japan Scientific Societies Press,Tokyo/S.Karger AG basel. 159-177 (1994)

[Publications] 小幡裕一: "生体防御における非古典的MHCクラスI分子の機能" 蛋白質・核酸・酵素臨時増刊号「エボリューション」. 39. 2626-2637 (1994)

[Publications] 堀寛: "自己-非自己識別機構の進化「生命体システムのなりたち」(小関治男、岡田節人編)" 講談社サイエンティフィック. 73-89 (1994)

[Publications] Salter-Cid,L.: "Hsp70 genes are kinked to the Xenopus major histocompatibility complex." Immunogenetics. 39. 1-7 (1994)

[Publications] Kasahara,M.: "Evolution of the major histocompatibility complex:A current overview." Transplant Immunol.2(in press). (1994)

[Publications] Kato,S.: "Isolation of the Xenopus complement factor B complementary DNA and linkage of the gene to the frog MHC." J.Immunol.153. 4546-4554 (1994)

[Publications] Kasahara,M.: "Mapping of acidic epididymal glycoprotein (Aeg) genes to mouse chromosome 17." Mammalian Genome. 5(in press). (1994)

[Publications] 笠原正典: "MHC遺伝子の起源と進化" 蛋白質・核酸・酵素. 39. 2606-2618 (1994)

[Publications] Haas,J.P.: "Polymorphism in the upstream regulatory regions of DQA1 genes and DRB1, QAP1,DQA1,DQB1 haplotypes in the German population." Hum.Immunol.39. 31-40 (1994)

[Publications] Koshizaka,T.: "A new HLA-DPB1 allele,DPB1^SUT(DPB1^4701)." Tissue Antigens.43. 50-53 (1994)

[Publications] Inoko,H.: "Role of human leukocyte antigens and T lymphocytes and in the immune response." Annals of Cancer Research and Therapy. 2. 173-191 (1994)

[Publications] Ogawa,K.: "A novel HLA-DPB1 allele,DPB1^3601(DPB1^KT)." Tissue Antigens. 44. 134-136 (1994)

[Publications] Sugaya,K.: "Three human MHC class III genes near the junction with the class II locus:gene for receptor of advanced glycosylation end products,HOX12 homeobox gene and a Notch-homolog,human counterpart of mouse mammary tumor gene int3." Genomics. 23. 408-419 (1994)

[Publications] Yoshino,M.: "No dose effect of recombinational hotspots in the mouse MHC." Immunogenetics. 39. 381-389 (1994)

[Publications] Yoshino,M.: "Recombination in the class III region of the mouse major histocompatibility complex." Immunogenetics. 40. 280-286 (1994)

[Publications] Hayasizaki,Y.: "Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method" Nature Genetics. 6. 33-40 (1994)

[Publications] Fukuda,Y.: "Negative effect of HLA-DQ antigen compatibility (Concordance on the survival of kidney grafts.)" Transplantation Proceedings. 26. 1887-1890 (1994)

[Publications] Yamamoto,K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA)class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice." J.Exp.Med.180. 165-171 (1994)

[Publications] Satoh,M.: "Genetic and immunological digfferences between Japanese patients with diffuse scleroderma and limited scleroderma." The Journal of Rheumatology. 21. 111-114 (1994)

[Publications] Takahata,N.: "Polymorphism at MHC loci and isolation by the immune system in vertebrates." (ed.B.Golding)in Non-neutral Evolution:Theories and Molecular Data(Chapman & Hall), 20 (1994)

[Publications] Moriwaki,K.: "Genetics in Wild mice." (eds.K.Moriwaki,T.Shiroishi,and H.Yonekawa)Japan Scientific Society Press, 333 (1994)

1994 Fiscal Year Annual Research Report

自己・非自己識別分子MHCの起源と進化

Principal Investigator

高畑 尚之 総合研究大学院大学, 教育研究交流センター, 教授 (30124217)

Research Products

[Publications] Takahata,N.: "Comments on the detection of reciprocal recombination or gene conversion." Immunogenetics. 39. 146-149 (1994)

[Publications] Satta,Y.: "Intensity of matural selection at the major histocompatibility complex loci." Proc.Natl.Acad.Sci.USA. 91. 7184-7188 (1994)

[Publications] Takahata,N.: "Divergence time and population size in the lineage leading to modern humans." Theor.Popul.Biol.(in press). (1995)

[Publications] Takahata,N.: "MHC diversity and selection." Immunological Review. (in press). (1995)

[Publications] Sugaya,K.: "Three genes in the human MHC class III region near the junction with the class II:gene for receptor of advanced glycosylation end products,PBX2 homeobox gene and a Norcth homolong,human counterpart of mouse mammary tumor gene int-3." Genomics. 23. 408-419 (1994)

[Publications] Matsumoto,K.: "The distribution of tenascin-X is distinct and often reciprocal to that of tenascin-C." J.Cell.Biol.125. 483-493 (1994)

[Publications] Ando,A.: "Cloning of a new kinesin‐related gene located at the centromeric end of the human MHC region." Immunogenetics. 39. 194-200 (1994)

[Publications] Yoshino,M.: "Recombination in the class III region of the mouse major histocompatibility complex." Immunogenetics. 40. 280-286 (1994)

[Publications] Morita,A.: "TL‐antigen as a transplantation antigen recognized by TL-restricted cytotoxic T cells." J.Exp.Med.179. 777-784 (1994)

[Publications] Obata,Y.: "The structure,function and evolution of mouse TL genes,nonclassical class I genes of the major histocompatibility complex." Proc,Natl.Acad.Sci.,USA. 91. 6589-6593 (1994)

[Publications] Obata,Y.: "TL genes in Asian wild mice.The evolutionary conserved nonclasical class I genes of the major histocompatibility complex.in Genetics in wild mice:its application to biomedical research." Japan Scientific Societies Press,Tokyo/S.Karger AG basel. 159-177 (1994)

[Publications] 小幡裕一: "生体防御における非古典的MHCクラスI分子の機能" 蛋白質・核酸・酵素 臨時増刊号「エボリューション」. 39. 2626-2637 (1994)

[Publications] 堀 寛: "自己-非自己識別機構の進化「生命体システムのなりたち」(小関治男、岡田節人 編)" 講談社サイエンティフィック. 73-89 (1994)

[Publications] Salter-Cid,L.: "Hsp70 genes are kinked to the Xenopus major histocompatibility complex." Immunogenetics. 39. 1-7 (1994)

[Publications] Kasahara,M.: "Evolution of the major histocompatibility complex:A current overview." Transplant Immunol.2(in press). (1994)

[Publications] Kato,S.: "Isolation of the Xenopus complement factor B complementary DNA and linkage of the gene to the frog MHC." J.Immunol.153. 4546-4554 (1994)

[Publications] Kasahara,M.: "Mapping of acidic epididymal glycoprotein (Aeg) genes to mouse chromosome 17." Mammalian Genome. 5(in press). (1994)

[Publications] 笠原 正典: "MHC遺伝子の起源と進化" 蛋白質・核酸・酵素. 39. 2606-2618 (1994)

[Publications] Haas,J.P.: "Polymorphism in the upstream regulatory regions of DQA1 genes and DRB1, QAP1,DQA1,DQB1 haplotypes in the German population." Hum.Immunol.39. 31-40 (1994)

[Publications] Koshizaka,T.: "A new HLA-DPB1 allele,DPB1^*SUT(DPB1^*4701)." Tissue Antigens.43. 50-53 (1994)

[Publications] Inoko,H.: "Role of human leukocyte antigens and T lymphocytes and in the immune response." Annals of Cancer Research and Therapy. 2. 173-191 (1994)

[Publications] Ogawa,K.: "A novel HLA-DPB1 allele,DPB1^*3601(DPB1^*KT)." Tissue Antigens. 44. 134-136 (1994)

[Publications] Sugaya,K.: "Three human MHC class III genes near the junction with the class II locus:gene for receptor of advanced glycosylation end products,HOX12 homeobox gene and a Notch-homolog,human counterpart of mouse mammary tumor gene int3." Genomics. 23. 408-419 (1994)

[Publications] Yoshino,M.: "No dose effect of recombinational hotspots in the mouse MHC." Immunogenetics. 39. 381-389 (1994)

[Publications] Yoshino,M.: "Recombination in the class III region of the mouse major histocompatibility complex." Immunogenetics. 40. 280-286 (1994)

[Publications] Hayasizaki,Y.: "Identification of an imprinted U2af binding protein related sequence on mouse chromosome 11 using the RLGS method" Nature Genetics. 6. 33-40 (1994)

[Publications] Fukuda,Y.: "Negative effect of HLA-DQ antigen compatibility (Concordance on the survival of kidney grafts.)" Transplantation Proceedings. 26. 1887-1890 (1994)

[Publications] Yamamoto,K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA)class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ transgenic mice." J.Exp.Med.180. 165-171 (1994)

[Publications] Satoh,M.: "Genetic and immunological digfferences between Japanese patients with diffuse scleroderma and limited scleroderma." The Journal of Rheumatology. 21. 111-114 (1994)

[Publications] Takahata,N.: "Polymorphism at MHC loci and isolation by the immune system in vertebrates." (ed.B.Golding)in Non-neutral Evolution:Theories and Molecular Data(Chapman & Hall), 20 (1994)

[Publications] Moriwaki,K.: "Genetics in Wild mice." (eds.K.Moriwaki,T.Shiroishi,and H.Yonekawa)Japan Scientific Society Press, 333 (1994)

高畑尚之総合研究大学院大学, 教育研究交流センター, 教授 (30124217)

[Publications] 小幡裕一: "生体防御における非古典的MHCクラスI分子の機能" 蛋白質・核酸・酵素臨時増刊号「エボリューション」. 39. 2626-2637 (1994)

[Publications] 堀寛: "自己-非自己識別機構の進化「生命体システムのなりたち」(小関治男、岡田節人編)" 講談社サイエンティフィック. 73-89 (1994)

[Publications] 笠原正典: "MHC遺伝子の起源と進化" 蛋白質・核酸・酵素. 39. 2606-2618 (1994)

[Publications] Koshizaka,T.: "A new HLA-DPB1 allele,DPB1^SUT(DPB1^4701)." Tissue Antigens.43. 50-53 (1994)

[Publications] Ogawa,K.: "A novel HLA-DPB1 allele,DPB1^3601(DPB1^KT)." Tissue Antigens. 44. 134-136 (1994)