1992 Fiscal Year Final Research Report Summary

HLAの分子医学生物学的研究

Research Project

Project/Area Number	02304037
Research Category	Grant-in-Aid for Co-operative Research (A)
Allocation Type	Single-year Grants
Research Field	Immunology
Research Institution	Kyushu University
Principal Investigator	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
Co-Investigator(Kenkyū-buntansha)	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)
Project Period (FY)	1990 – 1992
Keywords	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
Research Abstract	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。

Research Products

(34 results)

All Other

All Publications (34 results)

[Publications] Nishimura Y: "Expression of human MHC,HLA-DQW6 genes alter the immune response in C57BL/6" J Immunol. 145. 353-360 (1990)
[Publications] 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)
[Publications] Juji T: "HLA-homozygous donors and transfusion-associated graft-Versus-host disease" N Engl J Med. 322. 1007-1007 (1990)
[Publications] Kariyone A: "Functional expression of HLA-C blank antigens on human blood lymphocytes" J Immunol. 145. 3714-3718 (1990)
[Publications] Matsuki K: "HLA antigens in Japanese patients with Myasthenia Gravis" J Clin Invest. 86. 392-399 (1990)
[Publications] Kobata T: "A novel homodimeric molecule involved in human T cell activation" J Immunol. 144. 830-835 (1990)
[Publications] Yamamot J: "Presentation of human minor histocompatibiliyy antigens by HLA-B35 or HLA-B38 molecules" Proc Natl Acad Sci USA. 87. 2583-2587 (1990)
[Publications] Sekimata M: "Allodeterminatts and evolution of a novel HLA-B5 CREG antigen,HAL-SNA" J Immunol. 144. 3228-3233 (1990)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Hatae K: "Genetic control of non-responsiveness to hepatitis B Virus Vaccine by an extended HLA haplotype" Eur J Immunol. 22. 1899-1905 (1992)
[Publications] Senju S: "Allele-specific expression of the cytoplasmic exon of HLA-DQB1 gene" Immunogenetics. 36. 319-325 (1992)
[Publications] Kimura A: "DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA" Tissue Antigens. 40. 5-12 (1992)
[Publications] Yoshida M: "Polymerase chain reaction based analysis of polymorphism in the HLA-B gene" Hum Immunol. 34. 257-266 (1992)
[Publications] 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)
[Publications] Dong RP: "HLA-A and DPB1 loci confer susceptibility to Graves' disease" Hum Immunol. 35. 165-172 (1992)
[Publications] Harada H: "Sequencing and population analysis of four novel HLA-DPA1 alleles" Hum Immunol. 35. 173-178 (1992)
[Publications] Matsubara K: "A rapid and sensitive method for HLA-DRB1 typing by acridine-ester-labeled DNA probes" Hum Immunol. 35. 132-139 (1992)
[Publications] Inamitsu T: "Different recognition of transgenic HLA-DQw6 molecules by mouse CD4+ and CD8+ T cells" Immunogenetics. 35. 46-50 (1992)
[Publications] 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)
[Publications] Nomoto K: "Interference with cyclophosphamide-induced skin allograft tolerance by cyclosporin A" J Immunol. 149. 2668-2674 (1992)
[Publications] 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)
[Publications] Tanabe M: "Structural and functional analysis of monomorhpic determinants recognized by mAb reacting with HLA class Iα3 domin" J Immunol. 148. 1613-1618 (1992)
[Publications] Hill AVS: "Molecular analysis of the association of HLA-B53 and resistance to severe malaria" Nature. 360. 434-439 (1992)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Kawaguchi G: "Structural analysis of HLA-B40 epitopes" Hum Immunol.
[Publications] Kato N: "Molecular analysis of novel HLA-A33 subtype associated with HLA-B44" Tissue Antigen.
[Publications] Kata N: "Conservation of genes encoding HLA-B5,B35 cross reactive group antigens in various races" Hum Immunol.
[Publications] Sato K: "Evolution of the MHC:isolation of class II β-chain cDNA clones from the amphibian Xenopus Laevis" J Immunol.
[Publications] 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 Fiscal Year Final Research Report Summary

HLAの分子医学生物学的研究

Principal Investigator

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

Research Products

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

[Publications] 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)

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

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

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

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

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

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

[Publications] 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)

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

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

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

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

[Publications] 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)

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

[Publications] 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)

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

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

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

[Publications] 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.

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)