The exploration of cognate antigens, which induce drug or metal allergy by using soluble TCR

• Project/Area Number: 25670503
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Osaka University
• Principal Investigator: Arase Noriko 大阪大学, 医学(系)研究科(研究院), 特任研究員 (30360481)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 可溶型TCR / 金属アレルギー / 薬剤アレルギー / HLA / IV型アレルギー / 金属アレルギ―

Outline of Final Research Achievements

Recently, association between severe drug eruption and specific HLA allele has been identified, suggesting major role of T cell-immunity. T cell is also involved in metal allergy besides the activation of innate immunity. Whereas molecular mechanism how these small molecules to induce T cell response remains unclear. We considered that we could determine the nature of antigens by using recombinant solubilized T cell receptor αβ. At first, we developed recombinant TCR αβ chains specific for the certain peptide antigen. These TCR αβ chains react specifically to the peptide on antigen presenting cells. Next we established metal specific T cell clones, and confirmed the specificity of them. Thereafter, we established solubilized TCR αβ chains and analyzed the specificity. Unfortunately, these soluble TCR did not react specifically to the metal antigens. From these observations, it was revealed that method to produce soluble TCR for metal antigen need to be further optimized.

Research Products

• [Journal Article] ミスフォールドタンパク質/主要組織適合抗原複合体と自己免疫疾患(総説) (2016)
  • Author(s): 荒瀬規子、荒瀬尚
  • Journal Title: 日本臨床 Volume: 74(2) Pages: 359-368
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] LILRA2 is an innate immune sensor for microbially cleaved immunoglobulins. (2016)
  • Author(s): Hirayasu K, Saito F, Suenaga T, Shida K, Arase N, Oikawa K, Yamaoka T, Murota H, Chibana H, Nagai H, Nakamura Y, Katayama I, Colonna M, Arase H.
  • Journal Title: Nature Microbiology Volume: - Issue: 6 Pages: 1-7
  • DOI: 10.1038/nmicrobiol.2016.54
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Possible involvement of CCR4+CD8+ T cells and elevated serum CCL22 and CCL17 in Patients with Rhododenol-induced Leukoderma. (2015)
  • Author(s): Nishioka M, Tanemura A, Yang L, Tanaka A, Arase N, Katayama I
  • Journal Title: J Dermatol Sci. Volume: 77 Issue: 3 Pages: 188-190
  • DOI: 10.1016/j.jdermsci.2015.02.014
  • Peer Reviewed / Open Access
• [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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cellular misfolded proteins rescued from degradation by MHC class II molecules are possible targets for autoimmune diseases. (2015)
  • Author(s): Arase N, Arase H.
  • Journal Title: J Biochem. Volume: 158 Issue: 5 Pages: 367-372
  • DOI: 10.1093/jb/mvv093
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Autoantibodies to IgG/HLA class II complexes are associated with rheumatoid arthritis susceptibility (2014)
  • Author(s): Jin H, Arase N, Hirayasu K, Kohyama M, Suenaga T, Saito F, Tanimura K, Matsuoka S, Ebina K, Shi K, Toyama-Sorimachi N, Yasuda S, Horita T, Hiwa R, Takasugi K, Ohmura K, Yoshikawa H, Saito T, Atsumi T, Sasazuki T, Katayama I, Lanier LL, Arase H
  • Journal Title: Proceedings of National Academy of Science USA Volume: 111 Issue: 10 Pages: 3787-3792
  • DOI: 10.1073/pnas.1401105111
  • Peer Reviewed / Open Access
• [Journal Article] 自己免疫疾患の新たな発症メカニズム (2014)
  • Author(s): 荒瀬 規子、金 暉、荒瀬 尚
  • Journal Title: 細胞工学 Volume: 33 Pages: 762-763
• [Journal Article] 自己免疫疾患の新たな発症メカニズム (2014)
  • Author(s): 荒瀬 規子、金 暉、荒瀬 尚
  • Journal Title: 感染・炎症・免疫 Volume: 44 Pages: 67-69
• [Journal Article] Transport of misfolded endoplasmic reticulum proteins to the cell surface by MHC class II molecules. (2013)
  • Author(s): Jiang, Y., Arase, N., Kohyama, M., Hirayasu, K., Suenaga, T., Jin, H., Matsumoto, M., Shida, K., L. Lanier, L., Saito, T. and Arase, H.
  • Journal Title: Int. Immunol. Volume: 25 Issue: 4 Pages: 235-246
  • DOI: 10.1093/intimm/dxs155
  • Peer Reviewed
• [Journal Article] CD1a-positive familial cutaneous mastocytosis without germ-line or somatic mutations in c-kit (2013)
  • Author(s): Arase, N., Wataya-Kaneda, M., Oiso, N., Arase, H., Katayama, I.
  • Journal Title: Br. J. Dermatol. Volume: 169 Issue: 1 Pages: 201-204
  • DOI: 10.1111/bjd.12265
  • Peer Reviewed
• [Journal Article] Prevalence and impact of past history of food allergy in atopic dermatitis. (2013)
  • Author(s): Kijima A, Murota H, Takahashi A, Arase N, Yang L, Nishioka M, Yamaoka T, Kitaba S, Yamauchi-Takihara K, Katayama I.
  • Journal Title: Allergol. Int. Volume: 62 Pages: 105-112
  • NAID: 130004477175
  • Peer Reviewed
• [Journal Article] MHCクラス II 分子による細胞内ミスフォールド蛋白質の提示. (2013)
  • Author(s): 荒瀬規子、荒瀬 尚
  • Journal Title: 血液フロンティア Volume: 23 Pages: 1059-1065
• [Journal Article] 乳房針生検部より限局性強皮症を発症した例. (2013)
  • Author(s): 荒瀬規子、千田聡子、井川 健、片山一朗
  • Journal Title: 皮膚病診療 Volume: 35 Pages: 949-952
• [Journal Article] 一般病院における手湿疹患者の労働生産性，生活の質，医療費に関する検討 (2013)
  • Author(s): 荒瀬規子、村上有香子、高橋 彩、松井佐起、糸井沙織、山岡俊文、遠山知子、田中 文、片山一朗
  • Journal Title: Dermatol Cutan Allergol. Volume: 7 Pages: 87-92
  • NAID: 10031170804
  • Peer Reviewed
• [Presentation] メラノーマに対するHVJ-Eの抗腫瘍効果: ライブイメージングで見えたそのメカニズム (2016)
  • Author(s): 楊 怜悧、荒瀬規子、山岡俊文、揚 飛、金田眞理、種村 篤、室田浩之、片山一朗
  • Organizer: 第405回日本皮膚科学会北海道地方会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-19
• [Presentation] Presence of anti-β2GP1/HLA-DR complex autoantibodies in the non-APS patients with recurrent limb ulcerations. (2015)
  • Author(s): Noriko Arase, Kenji Tanimura, Jin Hui, Sumiko Matsuoka, Toshifumi Yamaoka, Megumi Nishioka, Eiji Kiyohara, Mamori Tani, Koichiro Ohmura, Hiroyuki Murota, Hisashi Arase, Ichiro Katayama
  • Organizer: 日本研究皮膚科学会 第40回学術大会・総会
  • Place of Presentation: 岡山
  • Year and Date: 2015-12-11
• [Presentation] Myeloperoxidase/HLA class II complexes are targets for autoantibodies in ANCA-associated vasculitis (2015)
  • Author(s): Hiwa Ryosuke, Ohmura Koichiro, Arase Noriko, Jin Hui, Hirayasu Kouyuki, Kohyama Masako, Suenaga Tadahiro, Saito Fumiji, Iwatani Hirotsugu, Atsumi Tatsuya, Terao Chikashi, Mimori Tsuneyo, Arase Hisashi
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] MHC class II molecules expose autoantibody epitopes on autoantigens. (2015)
  • Author(s): Hui Jin, Noriko Arase, Sumiko Matsuoka, Kouyuki Hirayasu, Masako Kohyama, Tadahiro Suenaga, Takehiko Sasazuki, Hisashi Arase.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] DIR is an innate immune sensor for microbially cleaved immunoglobulins. (2015)
  • Author(s): Kouyuki Hirayasu, Fumiji Saito, Tadahiro Suenaga, Kyoko Shida, Noriko Arase, Keita Oikawa, Toshifumi Yamaoka, Hiroyuki Murota, Hiroji Chibana, Ichiro Nakagawa, Tomoko Kubori, Hiroki Nagai, Yuji Nakamaru, Ichiro Katayama, Marco Colonna, Hisashi Arase.
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2015-11-18
• [Presentation] Novel autoantibody against the β2GP1/HLA-DR complex in patients with refractory cutaneous ulcerations. (2015)
  • Author(s): Noriko Arase, Hui Jin, Kenji Tanimura, Toshifumi Yamaoka, Eiji Kiyohara, Koichiro Ohmura, Hiroyuki Murota, Hisashi Arase, Ichro Katayama
  • Organizer: 14th International Workshop on Langerhans Cells
  • Place of Presentation: 京都
  • Year and Date: 2015-11-05
  • Int'l Joint Research
• [Presentation] MPO/HLA class II複合体は顕微鏡的多発血管炎における自己抗体の標的である (2015)
  • Author(s): 日和良介、大村浩一郎、荒瀬規子、金暉、平安恒幸、香山雅子、末永忠広、齋藤史路、岩谷博次、渥美達也、寺尾知可史、三森経世、荒瀬尚
  • Organizer: 第43回日本臨床免疫学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2015-10-22
• [Presentation] 難治性ロドデノール誘発性脱色素斑患者9例の臨床的検討 (2015)
  • Author(s): 髙橋 彩、楊 飛、楊 伶俐、永田由子、西岡めぐみ、荒瀬規子、種村 篤、片山一朗
  • Organizer: 第67回 日本皮膚科学会西部支部学術大会
  • Place of Presentation: 長崎
  • Year and Date: 2015-10-17
• [Presentation] ミスフォールドタンパク質ーHLAクラスII複合体と自己免疫疾患ー原因不明難治性皮膚潰瘍症例でのβ2GPI HLA-DR複合体抗体の検討ー (2015)
  • Author(s): 荒瀬規子、Hui Jin、谷村憲司、山岡俊文、室田浩之、荒瀬尚、片山一朗
  • Organizer: 第２２回分子皮膚科学フォーラム
  • Place of Presentation: 高知
  • Year and Date: 2015-04-17
• [Presentation] ミスフォールド蛋白質-MHC Class II複合体と自己免疫疾患 (2015)
  • Author(s): 荒瀬規子
  • Organizer: ケラチノサイトと免疫を勉強する会
  • Place of Presentation: 東京
  • Year and Date: 2015-03-28
• [Presentation] Inhibition of melanogenesis by HLA class II molecules. (2014)
  • Author(s): Arase N., Tanemura A., You R., Nishioka M., Jin H., Arase H., Katayama I.
  • Organizer: 日本研究皮膚科学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Analysis of CCR4-expressing T cells in patients with Rhododendrol-Induced Leukoderma. (2014)
  • Author(s): Nishioka M., Tanemura A., Tanaka A., Arase N., Nishikawa H., Katayama I., Sakaguchi S
  • Organizer: 日本研究皮膚科学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] MHC class II-restricted recognition of self-antigen/MHC class II complexes by autoantibodies. (2014)
  • Author(s): Jin H., Arase N., Matsuoka S., Hirayasu K., Kohayama M., Suenaga T., Nakamaru Y., Iwatani Y., Katayama I., Arase H.
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] Myeloperoxidase/HLA class II complexes are targets for autoantibodies in microscopic polyangiitis. (2014)
  • Author(s): Hiwa R., Ohmura K., Arase N., Jin H., Hirayasu K., Kohyama M., Suenaga T., Matsuoka S., Iwatani H., Atsumi T., Terao C., Mimori T., Arase H.
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2014-12-10 – 2014-12-12
• [Presentation] 一般病院における手湿疹患者の労働生産性、生活の質、医療費に関する検討 (2014)
  • Author(s): 荒瀬規子、村上有香子、高橋彩、松井佐起、越智沙織、 山岡俊文、遠山知子、田中 文、片山一朗
  • Organizer: 日本皮膚アレルギー・接触皮膚炎 学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2014-11-22 – 2014-11-24
• [Presentation] Immune sensing system for bacterially degraded immunoglobulin via activating receptor DIR (2014)
  • Author(s): Hirayasu K., Saito F., Nagai H., Shida K., Arase N., Horiguchi Y., Nakamaru Y., Katayama I., Arase H.
  • Organizer: あわじしま感染症・免疫フォーラム
  • Place of Presentation: 大阪
  • Year and Date: 2014-09-23 – 2014-09-24
• [Presentation] Analysis of Regulatory T Cells Fraction and CCR4-Expressing T Cells and Their PotentialFunction in Patients with Rhododenol-Induced Leukoderma (2014)
  • Author(s): Nishioka M., Tanemura A., Tanaka A., Arase N., Kanako T., Nishikawa H., Katayama I., Sakaguchi S.
  • Organizer: 世界色素細胞学会
  • Place of Presentation: Singapore
  • Year and Date: 2014-09-04 – 2014-09-07
• [Presentation] 4-(4-hydroroxyphenyl)-2-butanol (rhododendrol) activates autophagy-lysosome pathway in melanocytes: a potential mechanism for skin depigmentation disorder (2014)
  • Author(s): Lingli Yang, Mari Wataya-Kaneda, Fei Yang, Atsushi Tanemura, Noriko Arase, Ichiro Katayama
  • Organizer: 世界色素細胞学会
  • Place of Presentation: Singapore
  • Year and Date: 2014-09-04 – 2014-09-07
• [Presentation] 後天性白斑患者における自己抗体出現パターンの検討 (2014)
  • Author(s): 荒瀬規子、種村篤、金 暉、揚 伶俐、竹岡啓子、西田誠、瀧原圭子、日高洋、岩谷良則、荒瀬尚、片山一朗
  • Organizer: 日本皮膚科学会総会
  • Place of Presentation: 京都
  • Year and Date: 2014-05-30 – 2014-06-01
• [Presentation] MHCクラスⅡ分子によって細胞外へ輸送された細胞内ミスフォールド蛋白質が自己抗体の標的分子である (2014)
  • Author(s): 金暉、荒瀬規子、平安恒幸、香山雅子、末永忠広、松岡須美子、斉藤隆、Lewis L. Lanier、荒瀬尚
  • Organizer: Kyoto T cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2014-05-16 – 2014-05-17
• [Presentation] Three cases having both vitiligo and psoriasis, which are associated with autoimmune disease. (2013)
  • Author(s): Arase N, Tanemura A, Katayama I.
  • Organizer: 9th Asian Dermatological Congress
  • Place of Presentation: HongKong, China
• [Presentation] IgG heavy chain presented on HLA-DR is associated with rheumatoid arthritis susceptibility (2013)
  • Author(s): Hui Jin, Noriko Arase, Masako Kohyama, Fumiji Saito, Kouyuki Hirayasu, Maki Matsumoto, Kyoko Shida, Tadahiro Suenaga, Takashi Saito, Ichiro Katayama, Lewis L. Lanier & Hisashi Arase
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉 幕張
• [Presentation] β2-glycoprotein I presented on MHC class II molecules are recognized by autoantibodies in antiphospholipid syndrome. (2013)
  • Author(s): Kenji Tanimura, Tadahiro Suenaga, Hui Jin, Kouyuki Hirayasu, Noriko Arase, Masako Kohyama, Yasuhiko Ebina, Shinsuke Yasuda, Tetsuya Horita, Ichiro Katayama, Tatsuya Atsumi, Hideto Yamada, Hisashi Arase
  • Organizer: 日本免疫学会
  • Place of Presentation: 千葉 幕張
• [Book] WHAT'S NEW in 皮膚科学 2016-2017 (2016)
  • Author(s): 荒瀬規子 片山一朗
  • Total Pages: 236
  • Publisher: メディカルレビュー社
• [Patent(Industrial Property Rights)] 自己抗体の検出方法、自己免疫疾患の罹患の可能性を試験する方法、自己抗体の検出試薬および自己免疫疾患用の試験試薬 (2013)
  • Inventor(s): 荒瀬尚、荒瀬規子、谷村憲司、金暉
  • Industrial Property Rights Holder: 荒瀬尚、荒瀬規子、谷村憲司、金暉
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-04-01