Integrated redearch for HLA disease and evolution

2014 Fiscal Year Final Research Report

• Project Area: HLA 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 Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu 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)
• 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
• Keywords: ＨＬＡ / 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

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.

Free Research Field

人類遺伝学・免疫遺伝学