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Integrated redearch for HLA disease and evolution

Administrative Group

Project AreaHLA polymorphism, disease and evolution
Project/Area Number 22133001
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionKyushu University

Principal Investigator

SASAZUKI Takehiko  九州大学, 生体防御医学研究所, 特別主幹教授 (50014121)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Shigeyuki  独立行政法人理化学研究所, 横山構造生物学研究室, 上席研究員 (00159229)
SHIINA Takashi  東海大学, 医学部, 准教授 (00317744)
OKAMURA Tadashi  独立行政法人国立国際医療研究センター, 研究所, 実験動物管理室長 (00333790)
NISHIMURA Yasuharu  熊本大学, 大学院生命科学研究部(医), 教授 (10156119)
MORISHIMA Yasuo  愛知県がんセンター(研究所), 疫学予防部, 研究員 (20220056)
SATTA Yoko  総合研究大学院大学, 先導科学研究科, 教授 (20222010)
TOKUNAGA Katsushi  東京大学, 大学院医学系研究科(医学部), 教授 (40163977)
YAMAMOTO Ken  久留米大学, 医学部, 教授 (60274528)
IMANISHI Tadashi  東海大学, 医学部, 教授 (80270461)
猪子 英俊  東海大学, 医学部, 教授 (10101932)
平山 令明  東海大学, 医学部, 教授 (70238393)
Co-Investigator(Renkei-kenkyūsha) MIYADERA Hiroko  独立行政法人国立国際医療研究センター, 研究所, 上級研究員 (40361464)
MIZUKI Nobuhisa  横浜市立大学, 医学研究科, 教授 (90336579)
TANAKA Keiji  公益財団法人東京都医学総合研究所, 研究所, 所長 (10108871)
FUKUI Yoshinori  九州大学, 生体防御医学研究所, 教授 (60243961)
Research Collaborator INOKO Hidetoshi  
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥82,550,000 (Direct Cost: ¥63,500,000、Indirect Cost: ¥19,050,000)
Fiscal Year 2014: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2013: ¥19,760,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥4,560,000)
Fiscal Year 2012: ¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2011: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2010: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
KeywordsHLA / ゲノム多様性 / 立体構造 / 疾患感受性 / 疾患抵抗性 / 移植 / 自己免疫疾患 / 進化 / 疾病感受性 / データベース / HLA / 疾病 / ゲノム / HLA立体構造 / 自己免疫病
Outline of Final Research Achievements

We have conducted an integrated HLA research beyond the framework of the research field, and obtained following results. We developed a high-resolution new HLA typing method based on NGS, and published the HLA integrated database. We elucidated the three-dimensional structure of the cedar pollen antigen and HLA-DP5 complex. The significance of the stability of the HLA heterodimer in autoimmune disease onset was also elucidated. The effective peptide vaccine that induces both helper and killer T cells in tumor immunity has been developed. We have clarified that the ratio of non-synonymous substitution in PBR was diverse between HLA-DRB1 groups. We have identified new susceptibility loci, and the susceptible or protective HLA alleles for a number of autoimmune diseases. In unrelated bone marrow transplant, we identified the HLA mismatches which show the inhibitory effect to leukemia recurrence.

Report

(6 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (22 results)

All 2015 2014 2013 2012 2011 2010 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 4 results,  Acknowledgement Compliant: 4 results) Presentation (1 results) Remarks (3 results)

  • [Journal Article] Identification of a Hashimoto thyroiditis susceptibility locus via a genome-wide comparison with Graves' disease.2015

    • Author(s)
      Oryoji D, Ueda S, Yamamoto K, Yoshimura Noh J, Okamura K, Noda M, Watanabe N, Yoshihara A, Ito K, Sasazuki T.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 100 Issue: 2 Pages: E319-E324

    • DOI

      10.1210/jc.2014-3431

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] β2-glycoprotein I/ HLA class II complexes are novel autoantigens in antiphospholipid syndrome.2015

    • Author(s)
      Tanimura K, Jin H, Suenaga T, Morikami S, Arase N, Kishida K, Hirayasu K, Kohyama M, Ebina Y, Yasuda S, Horita T, Takasugi K, Ohmura K, Yamamoto K, Katayama I, Sasazuki T, Lanier LL, Atsumi T, Yamada H, Arase H.
    • Journal Title

      Blood

      Volume: 125 Issue: 18 Pages: 2835-2844

    • DOI

      10.1182/blood-2014-08-593624

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Biological significance of HLA locus matching in unrelated donor bone marrow transplantation.2015

    • Author(s)
      Morishima Y, Kashiwase K, Matsuo K, Azuma F, Morishima S, Onizuka M, Yabe T, Murata M, Doki N, Eto T, Mori T, Miyamura K, Sao H, Ichinohe T, Saji H, Kato S, Atsuta Y, Kawa K, Kodera Y, Sasazuki T; Japan Marrow Donor Program.
    • Journal Title

      Blood

      Volume: 125 Issue: 7 Pages: 1189-1197

    • DOI

      10.1182/blood-2014-10-604785

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Autoimmune susceptible HLA alleles encode unstable proteins.2015

    • Author(s)
      Miyadera, H., Ohashi, J., Lernmark, A., Kitamura, T., and Tokunaga, K.
    • Journal Title

      J. Clin. Invest.

      Volume: 125 Issue: 1 Pages: 275-291

    • DOI

      10.1172/jci74961

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural Basis for the Specific Recognition of the Major Antigenic Peptide from the Japanese Cedar Pollen Allergen Cry j 1 by HLA-DP5.2014

    • Author(s)
      Kusano S, Kukimoto-Niino M, Satta Y, Ohsawa N, Uchikubo-Kamo T, Wakiyama M, Ikeda M, Terada T, Yamamoto K, Nishimura Y, Shirouzu M, Sasazuki T, Yokoyama S.
    • Journal Title

      J Mol Biol.

      Volume: 426 Issue: 17 Pages: 3016-3027

    • DOI

      10.1016/j.jmb.2014.06.020

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] HLA-DRB1, -DRB3, -DRB4 and -DRB5 genotyping at a super-high resolution level by long range PCR and high-throughput sequencing.2014

    • Author(s)
      Ozaki Y, Suzuki S, Shigenari A, Okudaira Y, Kikkawa E, Oka A, Ota M, Mitsunaga S, Kulski JK, Inoko H, Shiina T.
    • Journal Title

      Tissue Antigens

      Volume: 83 Issue: 1 Pages: 10-16

    • DOI

      10.1111/tan.12258

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of independent susceptible and protective HLA alleles in Japanese autoimmune thyroid disease and their epistasis.2014

    • Author(s)
      Ueda S, Oryoji D, Yamamoto K, Noh JY, Okamura K, Noda M, Kashiwase K, Kosuga Y, Sekiya K, Inoue K, Yamada H, Oyamada A, Nishimura Y, Yoshikai Y, Ito K, Sasazuki T.
    • Journal Title

      J Clin Endocrinol Metab.

      Volume: 99 Issue: 2 Pages: E379-E383

    • DOI

      10.1210/jc.2013-2841

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Independent strong association of HLA-A*02:06 and HLA-B*44:03 with cold medicine-related Stevens-Johnson syndrome with severe mucosal involvement2014

    • Author(s)
      Ueta M, Kaniwa N, Sotozono C, Tokunaga K, Saito Y, Sawai H, Miyadera H, Sugiyama E, Maekawa K, Nakamura R, Nagato M, Aihara M, Matsunaga K, Takahashi Y, Furuya H, Muramatsu M, Ikezawa Z, Kinoshita S.
    • Journal Title

      Sci Rep.

      Volume: 4 Issue: 1 Pages: 4862-4862

    • DOI

      10.1038/srep04862

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of HLA-DR4 transgenic mice for the identification of CD4+ T cell epitopes of tumor-associated antigens.2013

    • Author(s)
      Yatsuda J, Irie A, Harada K, Michibata Y, Tsukamoto H, Senju S, Tomita Y, Yuno A, Hirayama M, Abu Sayem M, Takeda N, Shibuya I, Sogo S, Fujiki F, Sugiyama H, Eto M, Nishimura Y.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 12 Pages: e84908-e84908

    • DOI

      10.1371/journal.pone.0084908

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current perspectives on the intensity of natural selection of MHC loci.2013

    • Author(s)
      Yasukochi Y, Satta Y.
    • Journal Title

      Immunogenetics

      Volume: 65 Issue: 6 Pages: 479-483

    • DOI

      10.1007/s00251-013-0693-x

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population2012

    • Author(s)
      Okada Y, Terao C, Ikari K, Kochi Y, Ohmura K, Suzuki A, Kawaguchi T, Stahl EA, Kurreeman FA, Nishida N, Ohmiya H, Myouzen K, Takahashi M, Sawada T, Nishioka Y, Yukioka M, Matsubara T, Wakitani S, Teshima R, Tohma S, Takasugi K, Shimada K, Murasawa A, Honjo S, Matsuo K, Tanaka H, Tajima K, Suzuki T, Iwamoto T, Kawamura Y, Tanii H, Okazaki Y, Sasaki T, Gregersen PK, Padyukov L, Worthington J, Siminovitch KA, Lathrop M, Taniguchi A, Takahashi A, Tokunaga K, Kubo M, Nakamura Y, Kamatani N, Mimori T, Plenge RM, Yamanaka H, Momohara S, Yamada R, Matsuda F, Yamamoto K.
    • Journal Title

      Nat Genet.

      Volume: (in press) Issue: 5 Pages: 511-6

    • DOI

      10.1038/ng.2231

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genome-wide association analysis identifies new susceptibility loci for Behcet's disease and epistasis between HLA-B*51 and ERAP12012

    • Author(s)
      Mizuki N, Meguro A
    • Journal Title

      Nat Genet

      Volume: 45 Issue: 2 Pages: 202-7

    • DOI

      10.1038/ng.2520

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of independent risk loci for Graves' disease within the MHC in the Japanese population.2011

    • Author(s)
      Nakabayashi K, Shirasawa S
    • Journal Title

      J Hum Genet

      Volume: 56(11) Issue: 11 Pages: 772-778

    • DOI

      10.1038/jhg.2011.99

    • NAID

      10030661591

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fully human monoclonal antibody directed to proteolytic cleavage site in severe acute respiratory syndrome (SARS) coronavirus S protein neutralizes the virus in a rhesus macaque SARS model2011

    • Author(s)
      Miyoshi-Akiyama T, et al
    • Journal Title

      J Infect Dis

      Volume: 203 Issue: 11 Pages: 1574-1581

    • DOI

      10.1093/infdis/jir084

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oncogenic ras-induced down-regulation of pro-apoptotic protease caspase-2 is required for malignant transformation of intestinal epithelial cells2011

    • Author(s)
      Yoo BH, et al
    • Journal Title

      J Biol Chem

      Volume: 286 Issue: 45 Pages: 38894-38903

    • DOI

      10.1074/jbc.m111.290692

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nomenclature for factors of the HLA system, 2010.2010

    • Author(s)
      Marsh SG, et al.
    • Journal Title

      Tissue Antigens

      Volume: 75 Pages: 291-455

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An update to HLA nomenclature, 2010.2010

    • Author(s)
      Marsh SG, et al.
    • Journal Title

      Bone Marrow Transplant.

      Volume: 45 Pages: 846-848

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of highly conserved HLA haplotype on acute graft-versus-host disease.2010

    • Author(s)
      Morishima S, et al.
    • Journal Title

      Blood

      Volume: 115 Pages: 4664-4670

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Allelic variation in the protein stability of HLA-DQ shapes genetic predisposition to autoimmunity2012

    • Author(s)
      Miyadera H
    • Organizer
      16th International HLA and Immunogenetics Workshop and Conference/ 26th European Immunogenetics and Histocompatibility Conference
    • Place of Presentation
      Liverpool, England
    • Year and Date
      2012-05-28
    • Related Report
      2012 Annual Research Report
  • [Remarks] 新学術領域「HLA進化と疾病」

    • URL

      http://dbhla.jp/HP_sinryoiki/

    • Related Report
      2014 Annual Research Report
  • [Remarks] The HLA Information Resource (HLA-IR)

    • URL

      http://dbhla.jp/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 先端技術を駆使したHLA多型・進化・疾病に関する統合的研究

    • URL

      http://hp.hla-singakujyutsu.jp/

    • Related Report
      2012 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2019-07-29  

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