1992 年度研究成果報告書概要

HLAの分子医学生物学的研究

研究課題

研究課題/領域番号	02304037
研究種目	総合研究(A)
配分区分	補助金
研究分野	免疫学
研究機関	九州大学
研究代表者	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
研究分担者	雨宮浩国立小児病院, 小児医療研究センター, センター長 (80009563) 辻公美東海大学, 医学部, 教授 (30055834) 十字猛夫東京大学, 医学部, 教授 (20009997) 吉田孝人浜松医科大学, 医学部, 教授 (90041847) 柏木登北里大学, 医学部, 教授 (60095502)
研究期間 (年度)	1990 – 1992
キーワード	HLA / 遺伝的多型性 / 免疫応答 / 臓器移植 / 疾患感受性 / 多重遺伝子族 / 国際HLAワークショップ
研究概要	ヒトの主要組織適合抗原HLAは、高度の多型を示することにより、抗原性および免疫応答性の個体差を支配している。抗原性の個体差は、臓器移植に際して拒絶反応を惹起する。また、免疫応答性の個体差は、感染症ならびにそれに引きつづく感染症関連疾患や自己免疫症患への感受性あるいは抵抗性を支配することにより、疾病の重要な遺伝要因を形成している。本研究では、HLA領域内に存在する多数のHLA遺伝子群の構造解析と遺伝的多型性の解析、蛋白レベルでのHLA分子の多型性解析を行うことにより、HLA分子の発現調節機構、立体構造上の特徴、多型と連鎖不平衡の特徴の解明とその獲得機序の解析を行った。また、HLAの機能を解明するために、免疫応答の個体差とHLAとの関連、抗原ペプチドとHLA分子の結合特性、HLAと抗原ペプチドの複合体を認識するT細胞レセプターの構造およびT細胞の機能的サブセットを、ヒトおよびHLAトランスジェニックマウスを応用して解析した。さらに、多くの疾患を対象として、感受性あるいは抵抗性と最も強い相関を示すHLA対立遺伝子群を同定し、その構造的特徴を明らかにした。また複数のHLA分子間の相互作用による免疫応答性および自己免疫疾患との相関形成機序の存在を明らかにした。一方、臓器移植において、移植片の生着予後と移植ペア間のHLA一致性との関連を遺伝子レベルで明らかにし、生着予後の予見性におけるHLA分子の多型性解析の意義を確認した。本研究班での研究成果は、班員を中心としたメンバーによって企画された国際共同研究「第11回国際HLAワークショップ」において発表され、我国におけるHLA研究の先進性は国際的にきわめて高い評価を受けた。

研究成果
(34件)

すべてその他

すべて文献書誌 (34件)

[文献書誌] Nishimura Y: "Expression of human MHC,HLA-DQW6 genes alter the immune response in C57BL/6" J Immunol. 145. 353-360 (1990)
[文献書誌] Nezu N: "Regulation of HLA class II molecule expressions by IFN-γ:The signal transduction mechanism in glioblastoma cell lines" J Immunol. 145. 3126-3135 (1990)
[文献書誌] Juji T: "HLA-homozygous donors and transfusion-associated graft-Versus-host disease" N Engl J Med. 322. 1007-1007 (1990)
[文献書誌] Kariyone A: "Functional expression of HLA-C blank antigens on human blood lymphocytes" J Immunol. 145. 3714-3718 (1990)
[文献書誌] Matsuki K: "HLA antigens in Japanese patients with Myasthenia Gravis" J Clin Invest. 86. 392-399 (1990)
[文献書誌] Kobata T: "A novel homodimeric molecule involved in human T cell activation" J Immunol. 144. 830-835 (1990)
[文献書誌] Yamamot J: "Presentation of human minor histocompatibiliyy antigens by HLA-B35 or HLA-B38 molecules" Proc Natl Acad Sci USA. 87. 2583-2587 (1990)
[文献書誌] Sekimata M: "Allodeterminatts and evolution of a novel HLA-B5 CREG antigen,HAL-SNA" J Immunol. 144. 3228-3233 (1990)
[文献書誌] Kamikawaji N: "HLA-DQ restricted CD4+ T cells specific to streptococcal antigen exist in low responder but not in high responder" J Immunol. 146. 2560-2567 (1991)
[文献書誌] Fujisawa K: "High precursor frequency of human T cells reactive to HLA-DQ molecules expressed on mouse L cell transfectant" Eur J Immunol. 21. 2341-2347 (1991)
[文献書誌] Hiraiwa M: "T cell can recognize the allospecificites formed by the substitution of amino acid associated with HAL-Bw4/Bw6 epitopes" Hum Immunol. 32. 41-45 (1991)
[文献書誌] Hoshino S: "Polymerase chain reaction-single strand conformation polymorphism analysis of polymorphisms in DPA1 and DPB1 genes:a simple,economical and..." Hum Immunol. 33. 98-107 (1992)
[文献書誌] Hatae K: "Genetic control of non-responsiveness to hepatitis B Virus Vaccine by an extended HLA haplotype" Eur J Immunol. 22. 1899-1905 (1992)
[文献書誌] Senju S: "Allele-specific expression of the cytoplasmic exon of HLA-DQB1 gene" Immunogenetics. 36. 319-325 (1992)
[文献書誌] Kimura A: "DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA" Tissue Antigens. 40. 5-12 (1992)
[文献書誌] Yoshida M: "Polymerase chain reaction based analysis of polymorphism in the HLA-B gene" Hum Immunol. 34. 257-266 (1992)
[文献書誌] Odum N: "Signal transduction by HLA class II molecules in human T cells:induction of LFA-1-dependent and independent adhesion" Hum Immunol. 35. 71-84 (1992)
[文献書誌] Dong RP: "HLA-A and DPB1 loci confer susceptibility to Graves' disease" Hum Immunol. 35. 165-172 (1992)
[文献書誌] Harada H: "Sequencing and population analysis of four novel HLA-DPA1 alleles" Hum Immunol. 35. 173-178 (1992)
[文献書誌] Matsubara K: "A rapid and sensitive method for HLA-DRB1 typing by acridine-ester-labeled DNA probes" Hum Immunol. 35. 132-139 (1992)
[文献書誌] Inamitsu T: "Different recognition of transgenic HLA-DQw6 molecules by mouse CD4+ and CD8+ T cells" Immunogenetics. 35. 46-50 (1992)
[文献書誌] Ishiguro N: "A rat model of human T lymphocyte virus type I(HTLV-I)infection 1.Humoral antibody response,provirus integration,and HTLV-I-associated...." J Exp Med. 176. 981-989 (1992)
[文献書誌] Nomoto K: "Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A" J Immunol. 149. 2668-2674 (1992)
[文献書誌] Hiraiwa M: "Effect of the substitution in the helix and the sheet of HLA class I molecule on allorecognition of T cells specific for HLA B51 and HLA Bw53" Hum Immunol. 33. 82-88 (1992)
[文献書誌] Tanabe M: "Structural and functional analysis of monomorhpic determinants recognized by mAb reacting with HLA class Iα3 domin" J Immunol. 148. 1613-1618 (1992)
[文献書誌] Hill AVS: "Molecular analysis of the association of HLA-B53 and resistance to severe malaria" Nature. 360. 434-439 (1992)
[文献書誌] Uchigata Y: "Complete association with HLA-DR4 and insulin-processing to stimulate proliferation of autologous T cells in the insulin autoimmune..." Lancet. 340. 1467-1467 (1992)
[文献書誌] Imanishi T: "Distinctive patterns of nucleotide subsitution inferred from the phylogenies of the class I major histocompatibility complex genes" J Mol Evol. 35. 196-204 (1992)
[文献書誌] Fukui Y: "T cell repertoire in a transgenic C57BL/6 mice expressing the HLA-DRA gene on the X chromosome" Immunogenetics. 37. 204-211 (1992)
[文献書誌] Kawaguchi G: "Structural analysis of HLA-B40 epitopes" Hum Immunol.
[文献書誌] Kato N: "Molecular analysis of novel HLA-A33 subtype associated with HLA-B44" Tissue Antigen.
[文献書誌] Kata N: "Conservation of genes encoding HLA-B5,B35 cross reactive group antigens in various races" Hum Immunol.
[文献書誌] Sato K: "Evolution of the MHC:isolation of class II β-chain cDNA clones from the amphibian Xenopus Laevis" J Immunol.
[文献書誌] Obata F: "A single universal primer for the T-cell receptor (TCR)variable genes allows enzymatic amplification and direct sequencing of TCR cDNA of ..." Hum Immunol.

1992 年度 研究成果報告書概要

HLAの分子医学生物学的研究

研究代表者

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

研究成果

[文献書誌] Nishimura Y: "Expression of human MHC,HLA-DQW6 genes alter the immune response in C57BL/6" J Immunol. 145. 353-360 (1990)

[文献書誌] Nezu N: "Regulation of HLA class II molecule expressions by IFN-γ:The signal transduction mechanism in glioblastoma cell lines" J Immunol. 145. 3126-3135 (1990)

[文献書誌] Juji T: "HLA-homozygous donors and transfusion-associated graft-Versus-host disease" N Engl J Med. 322. 1007-1007 (1990)

[文献書誌] Kariyone A: "Functional expression of HLA-C blank antigens on human blood lymphocytes" J Immunol. 145. 3714-3718 (1990)

[文献書誌] Matsuki K: "HLA antigens in Japanese patients with Myasthenia Gravis" J Clin Invest. 86. 392-399 (1990)

[文献書誌] Kobata T: "A novel homodimeric molecule involved in human T cell activation" J Immunol. 144. 830-835 (1990)

[文献書誌] Yamamot J: "Presentation of human minor histocompatibiliyy antigens by HLA-B35 or HLA-B38 molecules" Proc Natl Acad Sci USA. 87. 2583-2587 (1990)

[文献書誌] Sekimata M: "Allodeterminatts and evolution of a novel HLA-B5 CREG antigen,HAL-SNA" J Immunol. 144. 3228-3233 (1990)

[文献書誌] Kamikawaji N: "HLA-DQ restricted CD4+ T cells specific to streptococcal antigen exist in low responder but not in high responder" J Immunol. 146. 2560-2567 (1991)

[文献書誌] Fujisawa K: "High precursor frequency of human T cells reactive to HLA-DQ molecules expressed on mouse L cell transfectant" Eur J Immunol. 21. 2341-2347 (1991)

[文献書誌] Hiraiwa M: "T cell can recognize the allospecificites formed by the substitution of amino acid associated with HAL-Bw4/Bw6 epitopes" Hum Immunol. 32. 41-45 (1991)

[文献書誌] Hoshino S: "Polymerase chain reaction-single strand conformation polymorphism analysis of polymorphisms in DPA1 and DPB1 genes:a simple,economical and..." Hum Immunol. 33. 98-107 (1992)

[文献書誌] Hatae K: "Genetic control of non-responsiveness to hepatitis B Virus Vaccine by an extended HLA haplotype" Eur J Immunol. 22. 1899-1905 (1992)

[文献書誌] Senju S: "Allele-specific expression of the cytoplasmic exon of HLA-DQB1 gene" Immunogenetics. 36. 319-325 (1992)

[文献書誌] Kimura A: "DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA" Tissue Antigens. 40. 5-12 (1992)

[文献書誌] Yoshida M: "Polymerase chain reaction based analysis of polymorphism in the HLA-B gene" Hum Immunol. 34. 257-266 (1992)

[文献書誌] Odum N: "Signal transduction by HLA class II molecules in human T cells:induction of LFA-1-dependent and independent adhesion" Hum Immunol. 35. 71-84 (1992)

[文献書誌] Dong RP: "HLA-A and DPB1 loci confer susceptibility to Graves' disease" Hum Immunol. 35. 165-172 (1992)

[文献書誌] Harada H: "Sequencing and population analysis of four novel HLA-DPA1 alleles" Hum Immunol. 35. 173-178 (1992)

[文献書誌] Matsubara K: "A rapid and sensitive method for HLA-DRB1 typing by acridine-ester-labeled DNA probes" Hum Immunol. 35. 132-139 (1992)

[文献書誌] Inamitsu T: "Different recognition of transgenic HLA-DQw6 molecules by mouse CD4+ and CD8+ T cells" Immunogenetics. 35. 46-50 (1992)

[文献書誌] Ishiguro N: "A rat model of human T lymphocyte virus type I(HTLV-I)infection 1.Humoral antibody response,provirus integration,and HTLV-I-associated...." J Exp Med. 176. 981-989 (1992)

[文献書誌] Nomoto K: "Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A" J Immunol. 149. 2668-2674 (1992)

[文献書誌] Hiraiwa M: "Effect of the substitution in the helix and the sheet of HLA class I molecule on allorecognition of T cells specific for HLA B51 and HLA Bw53" Hum Immunol. 33. 82-88 (1992)

[文献書誌] Tanabe M: "Structural and functional analysis of monomorhpic determinants recognized by mAb reacting with HLA class Iα3 domin" J Immunol. 148. 1613-1618 (1992)

[文献書誌] Hill AVS: "Molecular analysis of the association of HLA-B53 and resistance to severe malaria" Nature. 360. 434-439 (1992)

[文献書誌] Uchigata Y: "Complete association with HLA-DR4 and insulin-processing to stimulate proliferation of autologous T cells in the insulin autoimmune..." Lancet. 340. 1467-1467 (1992)

[文献書誌] Imanishi T: "Distinctive patterns of nucleotide subsitution inferred from the phylogenies of the class I major histocompatibility complex genes" J Mol Evol. 35. 196-204 (1992)

[文献書誌] Fukui Y: "T cell repertoire in a transgenic C57BL/6 mice expressing the HLA-DRA gene on the X chromosome" Immunogenetics. 37. 204-211 (1992)

[文献書誌] Kawaguchi G: "Structural analysis of HLA-B40 epitopes" Hum Immunol.

[文献書誌] Kato N: "Molecular analysis of novel HLA-A33 subtype associated with HLA-B44" Tissue Antigen.

[文献書誌] Kata N: "Conservation of genes encoding HLA-B5,B35 cross reactive group antigens in various races" Hum Immunol.

[文献書誌] Sato K: "Evolution of the MHC:isolation of class II β-chain cDNA clones from the amphibian Xenopus Laevis" J Immunol.

[文献書誌] Obata F: "A single universal primer for the T-cell receptor (TCR)variable genes allows enzymatic amplification and direct sequencing of TCR cDNA of ..." Hum Immunol.

1992 年度研究成果報告書概要

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)