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2006.9 ～2008.3 質量分析による患者血清からの脂質抗原迅速分析システムの開発 （独）新エネルギー・産業技術総合開発機構(NEDO)　産業技術実用化開発費補助事業「研究開発型ベンチャー技術開発助成事業」 

マイコプラズマ特異的脂質抗原解析やその合成法の特許、技術やノウハウなどの総合力共に他の追従を許さないものである。マイコプラズマに特化した研究・開発を進めており、抗原分子の物質特許および新たな抗原検索システム、遺伝子情報を有しており、総合力において有利。また、現在、産総研に研究拠点を置き、多くの大学の専門家、臨床病院との共同研究を実施している。マイコプラズマに特化した研究開発を行っており、患者検体からのマイコプラズマの分離培養法の構築、新たな遺伝子診断法の開発、特異抗体測定キットの開発を平行して行なっており、抗原測定法が加わればマイコプラズマを確実に診断する診断システムが構築できる。当社の事業はマイコプラズマ由来疾患に対し種々の診断システムを開発し、患者を選別し適切な医薬品を投与するために診断法と治療薬の総合的な医療システムの開発を目指している。その中でも、本事業は抗体測定によって選別された患者を抗原検出によって確定診断する重要な役割を担う中核技術に属する。   

2006.9 ～2009.3 生体内微量物質GGPL-Ⅲの発酵生産法及び高純度化法の開発 北海道ティー・エル・オー（株）、北海道大学との北海道経済産業局　戦略的基盤技術高度化支援事業


Mycoplasma lipid-antigens as immunoregulators in autoimmune diseasesKazuhiro Matsuda 1,2
1. National Institute of Advanced Industrial Science and Technology (AIST) AIST Tokyo Waterfront, Tokyo, Japan, 135-0064
2. Research and Development Department, M Bio Technology Incorporation, Tokyo, Japan, 135-8073

For the study of the innate immune response in infectious diseases and autoimmunity, as well as tumors, natural killer T (NKT) cells have become a major focus. Recognizing phospholipid and glycolipid antigens presented by CD1 molecules the novel T lymphocytes produce both Th1 and Th2 cytokines. Most mouse and human B cells express CD1d. Interactions between CD1d expressed on B cells and CD1d-restricted T cells may play a role in determining amount, isotype, and specificity of the antibodies produced.
Mycoplasmas have been reported as pathogens of autoimmune diseases, rheumatic diseases, asthma, neurological disorders, so on. Anti-glycolipid, such as Gal-cer, antibodies are reported to be present in the patients of autoimmune diseases with preceding mycoplasma infection. Mycoplasma lipid-antigens induce anti-mycoplasma antibodies, and they also act as autoantibodies. We have succeeded to determine the structures of the lipid-antigens, and revealed molecular mimicry. These lipid-antigens may be useful for the analysis of the signaling mechanism bridging innate and acquired immunity.




1. Kawahito, Y., Ichinose, S., Sano, H., Tsubouchi, Y., Kohno, M., Yoswhikawa, T., Tokunaga, D., Hojo, T., Harawsawa, R., Nakano, T., Matsuda K. Mycoplasma fermentans glycolipid-antigen as a pathogen of rheumatoid arthritis. Biochemical and Biophysical Communication 369 : 561-566 (2008)

2. 松田和洋、只野―有富桂子、飯田―田中直子、新宮佑子、富山哲雄、原澤　亮、森田大児、楠　進　神経障害因子誘導に関わるMycoplasma pneumonie 特異脂質抗原の構造解析　日本マイコプラズマ学会雑誌　第34号　45-46 (2007)

3. Matsuda, K. Lipid antigen. Encyclopedia of Life Science 2nd edition, Nature publishing group (in press)

4. Matsuda, K. Mycoplasma fermentans and rheumatoid arthtritis: from the structural analysis of choline-containing glycoglycerophospholipids of Mycoplasma fermentans for the regulation of the immune system and the drug discovery. 日本マイコプラズマ学会雑誌 第31号 35-36 (2004)

5. Matsuda, K. Phosphocholine-containing glycoglycerolipids of Mycoplasma fermentans as a pathogen of rheumatoid arthritis: Possible role of Mycoplasma fermentans GGPLs in the pathogenesis of neuroendocrine-immune abnormalities. Recent. Res. Devel. Neurosci. 1: 15-23 (2004)

6. 松田和洋　特集マイコプラズマ感染症の基礎と臨床　慢性関節リウマチの関節破壊原因物質としてのMycoplasma fermentans  特異コリン含有糖リン脂質　微生物と臨床 30: 75-79 (2003)    

7. Matsuda, K., Saito, M., Yamamoto, N. Lipid antigen Encyclopedia of Life Science, Nature publishing group, vol.1 pp748-755. (2002)

8. Matsuda, K., Li, J.L., Shizuko, I., Ryo, H., Saito, M., Yamamoto, N. Monoclonal antibody against Mycoplasma fermentans-specific aminoglycoglycerolipid. Microbiol. Immunol.  44: 695-702 (2000)

9. Matsuda, K., Ishizuka, I., Kasama, T., Handa, S., Yamamoto, T., Taki, T. Structure of phosphocholine-containing aminoglycoglycerolipids: a novel lipid antigen of Mycoplasma fermentans. Biochim. Biophys. Acta 1349: 1-12　(1997)

10. Matsuda, K., Li, J.L., Harasawa, R., Yamamoto, N. Phosphocholine-containing glycoglycerolipids (GGPL-I and GGPL-III) are species-specific major immunodeterminants of Mycoplasma fermentans. Biochem. Biophys. Res. Com. 233: 644-649 (1997)

11. Matsuda, K., Harasawa, R., Li, J.L., Kasama, T., Taki, T., Handa, S., Yamamoto, N. Identification of phosphocholine-containing glycoglycerolipids purified from Mycoplasma fermentans-infected human helper T-cell culture as components of M. fermentans. Microbiolo. Immunol. 39: 307-313 (1995)

12. Matsuda, K., Kasama, T., Ishizuka, I., Handa, S., Yamamoto, N., Taki, T. Structure of a novel phosphocholine-containing glycoglycerolipid from Mycoplasma fermentans. J. Biol. Chem. 269: 33123-33128 (1994)

13. Matsuda, S., Matsuda, K., Ito, Y. Separation of phospholipids and glycolipids using analytical toroidal-coil countercurrent chromatography. II. Comparison of the hydrophobicity between Mycoplasma fermentans  and human-brain lipids. J. Liq. Chrom. & Rel. Technol. 26: 1135-1147 (2003)

14. 松田和洋　第４回２１世紀の境界領域を考えるシンポジウム　リウマチ新規診断・治療薬の開発：慢性関節リウマチの関節破壊原因物質であるマイコプラズマ由来グライコ脂質の発見. 19: 17-24 (2002)

15. Shingu, Y., Nishida, Y., Dohi, K., Matsuda, K., Kobayashi, K. Converient access to halide ion-catalyzed alpha-glycosylation free from noxious fumes at the donor synthesis. J. Carbohydr. Chem. 21: 605-611 (2002)

16. Matsuda, K., Matsuda, S., Saito, M., Ito, Y. Separation of phospholipids and glycolipids using analytical toroidal-coil countercurrent chromatography. I. Separation of human brain lipids. J. Liq. Chrom. & Rel. Technol. 25: 1267-1281 (2002)

17. 松田和洋 特別講演総説 Mycoplasma fermentans  特異的糖リン脂質抗原の構造解析とその意義日本マイコプラズマ学会誌　第28号 1-10 (2001)

18. Nishida, Y., Takamori, Y., Ohrui, H., Ishizuka, I., Matsuda, K., Kobayashi, K. Synthesis and absolute configulation of a novel aminoglycoglycerolipid, species-specific immunodeterminant of Mycoplasma fermentans. Tetrahedron lett. 40: 2371-2374 (1999)

19. Shingu, Y., Nishida, Y., Dohi, K., Matsuda, K., Kobayashi, K. Converient access to halide ion-catalyzed alpha-glycosylation free from noxious fumes at the donor synthesis. J. Carbohydr. Chem. 21: 605-611 (2002)

20. Nishida, Y., Takamori, Y., Ohrui, H., Ishizuka, I., Matsuda, K., Kobayashi, K. Synthesis and absolute configulation of a novel aminoglycoglycerolipid, species-specific immunodeterminant of Mycoplasma fermentans. Tetrahedron lett. 40: 2371-2374 (1999)

21. Nishida, Y., Takamori, Y., Matsuda, K., Ohrui, H., Yamada, T., Kobayashi, K. Synthesis of artificial glycoconjugate polymer carrying 6-O-phosphocholine--D-glucopyranoside, biological active segment of main cell membrane glycolipids of Mycoplasma fermentans. J. Carbohydr. Chem. 18: 65-72 (1999)

22. Li, J.L., Matsuda, K., Takagi, M., Yamamoto, N.  Detection of serum antibodies against phosphocholine-containing aminoglycoglycerolipid specific to Mycoplasma fermentans in HIV-1 infected individual. J. Immunol. Methods 208: 103-113 (1997)

23. Nishida, Y., Ohrui, H., Meguro, H., Ishizawa, M., Matsuda, K., Taki, T., Handa, S., Yamamoto, N. Synthesis and absolute configuration of 6-O-phosphocholine--D-glucopyranosyl glycerolipid isolated from HTLV-I-infected cell lines. Tetrahedron Lett. 35: 5465-5468 (1994)

24. Matsuda, K., Taki, T., Hamanaka, S., Kasama, T., Rokukawa, C., Handa, S., Yamamoto, N. Glycosphingolipid compositions of human T-lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV)-infected cell lines. Biochim Biophys Acta 1168: 123-129 (1993)

25. Matsuda, K., Yamamoto, N., Kaneko, T., Iwahashi, M., Hashimoto, S., Araki, K. Hypercalcemia and serum TNF-α in T-cell leukaemia. Lancet 335(8696): 1032 (1990)

26. Kitamura, K., Matsuda, K., Ide, M., Tokunaga, T., Honda, M. A fluorescence sandwich ELISA for detecting soluble and cell-associated human interleukin-2.  J. Immunol. Methods 121: 281-288 (1990)

27. Honda, M., Kitamura, K., Matsuda, K., Yokota, Y., Yamamoto, N., Mitsuyasu, R., Chermann, J.C., Tokunaga, T. Soluble IL-2 receptor in AIDS: correlation of its serum level with the classification of HIV-induced diseases and its characterization. J. Immunol. 142: 4248-4255 (1989)