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Diversity in HLA heterodimers

Planned Research

Project AreaHLA polymorphism, disease and evolution
Project/Area Number 22133006
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 InstitutionResearch Institute, International Medical Center of Japan (2013-2014)
The University of Tokyo (2010-2012)

Principal Investigator

MIYADERA Hiroko  独立行政法人国立国際医療研究センター, その他部局等, その他 (40361464)

Co-Investigator(Kenkyū-buntansha) HITOMI Yuki  東京大学, 大学院医学系研究科, 助教 (10525819)
Project Period (FY) 2010-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥45,240,000 (Direct Cost: ¥34,800,000、Indirect Cost: ¥10,440,000)
Fiscal Year 2014: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2012: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
Fiscal Year 2011: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2010: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywordsヒト白血球抗原(HLA) / 主要組織適合性抗原(MHC) / HLA / MHC / 自己免疫 / 免疫遺伝
Outline of Final Research Achievements

Variations in human leukocyte antigens (HLA) are strongly associated with immune-related disorders including autoimmune diseases and infections, among others. However, underlying mechanism has remained elusive for most of HLA-associated diseases. In this study, we aimed to uncover the mechanism of HLA association with autoimmune and other HLA-associated disorders. We have established a protocol to estimate allelic differences in the protein stability of HLA. Using this method, we analyzed the stability of diverse HLA-DQ allele products and found that HLA-DQ alleles that are associated with susceptibility to type 1 diabetes encoded extremely unstable proteins. Our finding suggests that a novel mechanistic basis might operate in the development of autoimmune diseases.

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

    (47 results)

All 2015 2014 2013 2012 2011 2010

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (41 results) Patent(Industrial Property Rights) (1 results)

  • [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] 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

    • URL

      https://pure.teikyo.jp/en/publications/6f008634-2fec-4098-9778-3bf0f47687a5

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In silico risk assessment of HLA-A*02:06-associated Stevens-Johnson syndrome and toxic epidermal necrolysis caused by cold medicine ingredients.2013

    • Author(s)
      Isogai H, Miyadera H, Ueta M, Sotozono C, Kinoshita S, Tokunaga K, Hirayama N
    • Journal Title

      J Toxicol.

      Volume: Article ID 514068 Pages: 514068-514068

    • DOI

      10.1155/2013/514068

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HLA-DQ association and allele competition in Chinese narcolepsy.2012

    • Author(s)
      Han F
    • Journal Title

      Tissue Antigens.

      Volume: 80 Issue: 4 Pages: 328-335

    • DOI

      10.1111/j.1399-0039.2012.01948.x

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Abnormally low serum acylcarnitine levels in narcolepsy patients2011

    • Author(s)
      宮川卓、宮寺浩子, 他
    • Journal Title

      Sleep

      Volume: 34 Pages: 349-353

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] MHC-peptide interaction analysis by the cell-surface expression assay2014

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都国際会議場(京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Preparation of recombinant HLA-A*31:01 and mutants to determine the interaction of carbamazepine with HLA-A2014

    • Author(s)
      Azzaya Enkbayar、宮寺浩子、徳永勝士、他
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      京都国際会議場(京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] HLA-peptide binding analysis by the cell-surface expression assay2014

    • Author(s)
      宮寺浩子、徳永勝士、他
    • Organizer
      第40回米国組織適合性学会
    • Place of Presentation
      米国 デンバー
    • Year and Date
      2014-10-20 – 2014-10-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] HLAタンパク質細胞表面発現量測定による HLA-ペプチド相互作用の評価2014

    • Author(s)
      宮寺浩子、徳永勝士、他
    • Organizer
      第23回日本組織適合性学会大会
    • Place of Presentation
      長崎大学
    • Year and Date
      2014-09-13 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Preparation of recombinant HLA-A*31:01 and mutants to determine the interaction of carbamazepine with HLA-A2014

    • Author(s)
      Azzaya Enkbayar、宮寺浩子、徳永勝士、他
    • Organizer
      第23回日本組織適合性学会大会
    • Place of Presentation
      長崎大学
    • Year and Date
      2014-09-13 – 2014-09-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Allelic diversity in HLA class II protein stability shapes HLA evolution and disease association2013

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2013-12-11 – 2013-12-13
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional analysis of HLA-DQ protein and peptide interaction to understand autoimmune mechanism of Narcolepsy.2013

    • Author(s)
      陳 萱蓉、宮寺浩子、徳永勝士
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2013-12-11 – 2013-12-13
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional analysis HLA-A*02:06, the risk allele for Stevens-Johnson syndrome with ocular complication in Japanese2013

    • Author(s)
      Azzaya Enkbayar、宮寺浩子、徳永勝士
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県)
    • Year and Date
      2013-12-11 – 2013-12-13
    • Related Report
      2013 Annual Research Report
  • [Presentation] HLA class II タンパク質安定性のアリル間多様性とHLAの進化2013

    • Author(s)
      宮寺浩子、大橋順、徳永勝士
    • Organizer
      日本人類遺伝学会第58回大会
    • Place of Presentation
      江陽グランドホテル(仙台市)
    • Year and Date
      2013-11-20 – 2013-11-23
    • Related Report
      2013 Annual Research Report
  • [Presentation] Expression of recombinant HLA-A*31:01 and mutant alleles to determine interaction of carbamazepine with HLA-A2013

    • Author(s)
      Azzaya Enkbayar、宮寺浩子、徳永勝士、他
    • Organizer
      第22回日本組織適合性学会大会
    • Place of Presentation
      コラッセ福島(福島市)
    • Year and Date
      2013-09-14 – 2013-09-16
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional analysis of HLA-DQ protein and peptide interaction to understand autoimmune mechanism of Narcolepsy.2013

    • Author(s)
      陳 萱蓉、宮寺浩子、徳永勝士
    • Organizer
      第22回日本組織適合性学会大会
    • Place of Presentation
      コラッセ福島(福島市)
    • Year and Date
      2013-09-14 – 2013-09-16
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of HLA-DR9 protein and peptide interaction in association to type 1 diabetes in Japanese2013

    • Author(s)
      Chen, Cindy Chia Jung、宮寺浩子、徳永勝士
    • Organizer
      第22回日本組織適合性学会大会
    • Place of Presentation
      コラッセ福島(福島市)
    • Year and Date
      2013-09-14 – 2013-09-16
    • Related Report
      2013 Annual Research Report
  • [Presentation] Evolution of HLA class II through diversification in protein stability levels2013

    • Author(s)
      宮寺浩子、大橋順、徳永勝士
    • Organizer
      第100回米国免疫学会
    • Place of Presentation
      米国 ハワイ
    • Year and Date
      2013-05-03 – 2013-05-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] Analysis of HLA-DR protein and peptide interaction in association to type 1 diabetes in Japanese.2013

    • Author(s)
      Chen, Cindy Chia Jung, 宮寺浩子、徳永勝士
    • Organizer
      第100回米国免疫学会
    • Place of Presentation
      米国 ハワイ
    • Year and Date
      2013-05-03 – 2013-05-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] Functional analysis of HLA-DQ protein and peptide interaction in association to autoimmune mechanism of Narcolepsy.2013

    • Author(s)
      陳 萱蓉、宮寺浩子、徳永勝士
    • Organizer
      第100回米国免疫学会
    • Place of Presentation
      米国 ハワイ
    • Year and Date
      2013-05-03 – 2013-05-06
    • Related Report
      2013 Annual Research Report
  • [Presentation] HLA^A*31:01が関与するカルバマゼピンの副作用発現の分子機構2013

    • Author(s)
      宮寺浩子
    • Organizer
      日本薬学会第133回年会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2013-03-27
    • Related Report
      2012 Annual Research Report
  • [Presentation] Allelic variations in the protein stability of HLA determine genetic risks for type 1 diabetes2012

    • Author(s)
      宮寺浩子
    • Organizer
      第41回日本免疫学会学術集会
    • Place of Presentation
      神戸国際会議場 (兵庫県神戸市)
    • Year and Date
      2012-12-05
    • Related Report
      2012 Annual Research Report
  • [Presentation] Allelic variation in the protein stability of HLA shapes genetic association of HLA with type 1 diabetes.2012

    • Author(s)
      宮寺浩子
    • Organizer
      米国人類遺伝学会第62回大会
    • Place of Presentation
      米国(サンフランシスコ)
    • Year and Date
      2012-11-06
    • Related Report
      2012 Annual Research Report
  • [Presentation] HLA-DQタンパク質安定性と一型糖尿病感受性・抵抗性との関連2012

    • Author(s)
      宮寺浩子
    • Organizer
      日本人類遺伝学会第57回大会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2012-10-24
    • Related Report
      2012 Annual Research Report
  • [Presentation] HLA-DQタンパク質安定性と一型糖尿病疾患感受性・抵抗性との関連2012

    • Author(s)
      宮寺浩子
    • Organizer
      第21回日本組織適合性学会大会
    • Place of Presentation
      明治大学 (東京都千代田区)
    • Year and Date
      2012-09-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] ALLELIC VARIATION IN THE PROTEIN STABILITY OF HLA-DQ SHAPES GENETIC PREDISPOSITION TO AUTOIMMUNITY2012

    • Author(s)
      宮寺浩子
    • Organizer
      第16回国際HLAワークショップ、第26回欧州組織適合性学会合同大会
    • Place of Presentation
      英国(リバプール)
    • Year and Date
      2012-05-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] HLA-DQ trans heterodimer association to type 1 diabetes in East Asian population2012

    • Author(s)
      宮寺浩子
    • Organizer
      第99回米国免疫学会
    • Place of Presentation
      米国(ボストン)
    • Year and Date
      2012-05-04
    • Related Report
      2012 Annual Research Report
  • [Presentation] 慢性B型肝炎感受性・抵抗性に関連するHLA-DPの機能解析2011

    • Author(s)
      高柳彩、宮寺浩子、徳永勝士
    • Organizer
      第34回日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Preparation of MHC class II tetramer (DR04:06) for autoreactive CD4+ T cells detection2011

    • Author(s)
      内田優輝、宮寺浩子、徳永勝士
    • Organizer
      第34回日本分子生物学会大会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Preparation of MHC class II tetramer (DR04:06) for autoreactive CD4+ T cells detection2011

    • Author(s)
      内田優輝、宮寺浩子、徳永勝士
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県千葉市)
    • Year and Date
      2011-11-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 1型糖尿病疾患感受性とHLA-DQ多型の関連メカニズム2011

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県千葉市)
    • Year and Date
      2011-11-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 慢性B型肝炎感受性・抵抗性に関連するHLA-DPの機能解析2011

    • Author(s)
      高柳彩、宮寺浩子、徳永勝士
    • Organizer
      第40回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ(千葉県千葉市)
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] ナルコレプシー感受性・抵抗性とHLA-DQトランス型二量体形成2011

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      日本人類遺伝学会第56回大会
    • Place of Presentation
      幕張メッセ(千葉県千葉市)
    • Year and Date
      2011-11-10
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mechanisms of HLA-DQ predispositions to type 1 diabetes in European and East Asian populations2011

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      米国人類遺伝学会第61回大会
    • Place of Presentation
      カナダ・モントリオール
    • Year and Date
      2011-10-13
    • Related Report
      2011 Annual Research Report
  • [Presentation] 慢性B型肝炎感受性・抵抗性に関連するHLA-DPの機能解析2011

    • Author(s)
      高柳彩、宮寺浩子、徳永勝士
    • Organizer
      第20回日本組織適合性学会大会
    • Place of Presentation
      ツインメッセ静岡(静岡県静岡市)
    • Year and Date
      2011-08-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] HLAクラスIIテトラマーの調製を目的としたHLA-DRA*01:01/DRB1*04:06の発現2011

    • Author(s)
      内田優輝、宮寺浩子、徳永勝士
    • Organizer
      第20回日本組織適合性学会大会
    • Place of Presentation
      ツインメッセ静岡(静岡県静岡市)
    • Year and Date
      2011-08-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] ナルコレプシー感受性、抵抗性とHLA-DQトランス型二量体形成2011

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      第20回日本組織適合性学会大会
    • Place of Presentation
      ツインメッセ静岡(静岡県静岡市)
    • Year and Date
      2011-08-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] HLA class II (HLA-DQ) protein stability profile and disease association2011

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      米国免疫学会第98回年会
    • Place of Presentation
      米国・サンフランシスコ
    • Year and Date
      2011-05-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] Expression of recombinant HLA-DRA*0101/DRB1*0406 and preparation of HLA class II tetramer2010

    • Author(s)
      内田優輝、宮寺浩子, 他
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Functional analysis of HLA-DP, associated with the susceptibility to chronic hepatitis B2010

    • Author(s)
      高柳彩、宮寺浩子, 他
    • Organizer
      第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] HLAクラスIIタンパク質のヘテロ二量体形成と機能的多様性2010

    • Author(s)
      宮寺浩子、徳永勝士
    • Organizer
      日本人類遺伝学会第55回大会
    • Place of Presentation
      大宮ソニックシティ(埼玉県さいたま市)
    • Year and Date
      2010-10-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] HLAクラスIIテトラマーの調製を目的としたHLA-DRA*0101/DRB1*0406の発現2010

    • Author(s)
      内田優輝、宮寺浩子, 他
    • Organizer
      日本人類遺伝学会第55回大会
    • Place of Presentation
      大宮ソニックシティ(埼玉県さいたま市)
    • Year and Date
      2010-10-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] HLAクラスIIテトラマーの調製を目的としたHLA-DRA*0101/DRB1*0406の発現2010

    • Author(s)
      内田優輝、宮寺浩子, 他
    • Organizer
      第19回日本組織適合性学会大会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2010-09-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] 慢性B型肝炎感受性・抵抗性に関連するHLA-DPの機能解析2010

    • Author(s)
      高柳彩、宮寺浩子, 他
    • Organizer
      第19回日本組織適合性学会大会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2010-09-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] HLAクラスIIタンパク質の多様性2010

    • Author(s)
      宮寺浩子
    • Organizer
      第19回日本組織適合性学会大会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2010-09-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Expression of HLA-DRA*0101/DRB1*0406 for the preparation of HLA class II tetramer2010

    • Author(s)
      内田優輝、宮寺浩子, 他
    • Organizer
      第14回国際免疫学会
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 新規安定化組換えMHCタンパク質2010

    • Inventor(s)
      宮寺浩子, 徳永勝士
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Number
      2010-274207
    • Filing Date
      2010-12-09
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2018-09-21  

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