臨床検査49巻7号

2005年07月発行

今月の主題 アレルギー疾患の現況と今後の展望 総説

ダニ主要アレルゲンの構造・機能とIgE

著者： 高井敏朗¹

所属機関： ¹順天堂大学医学部アトピー疾患研究センター

ページ範囲：P.739 - P.747

〔SUMMARY〕　ハウスダスト中のダニは，喘息，アトピー性皮膚炎，鼻炎などの様々なアレルギー疾患にかかわる重要なアレルゲンである．本稿では，アレルゲンとダニアレルゲンに関する基本知識を簡単に解説した後，ダニ主要アレルゲンに関して，「アレルゲンの構造」vs「IgE結合」，および「アレルゲンの機能」vs「アレルギー疾患誘導」という2つの切り口で最近の研究の流れを整理・紹介してみたい．〔臨床検査　49：739-747，2005〕

参考文献

１) Thomas WR, Smith WA, Hales BJ, et al：Characterization and immunobiology of house dust mite allergens. Int Arch Allergy Immunol　29：1-18, 2002

２) Valenta R：The future of antigen-specific immunotherapy of allergy. Nature Rev Immunol　2：446-453, 2002

３) Chua KY, Stewart GA, Thomas WR, et al：Sequence analysis of cDNA coding for a major house dust mite allergen, Der p 1. Homology with cysteine proteases. J Exp Med 167：175-182, 1988

４) Yuuki T, Okumura Y, Ando T, et al：Cloning and sequencing of cDNA corresponding to mite major allergen Der f II. Arerugi　39：557-561, 1990

５) Ichikawa S, Hatanaka H, Yuuki T, et al：Solution structure of Der f 2, the major mite allergen for atopic diseases. J Biol Chem　273：356-360, 1998

６) Mueller GA, Benjamin DC, Rule GS. Tertiary structure of the major house dust mite allergen Der p 2；sequential and structural homologies. Biochemistry　37：12707-12714, 1998

７) van Neerven RJ, Ebner C, Yssel H, et al：T-cell responses to allergens：epitope-specificity and clinical relevance. Immunol Today　17：526-532, 1996

８) Matsuoka T, Kohrogi H, Ando M, et al：Dermatophagoides farinae-1-derived peptides and HLA molecules recognized by T cells from atopic individuals. Int Arch Allergy Immunol　112：365-370, 1997

９) Inoue R, Matsuoka T, Kondo N, et al：Identification of Dermatophagoides farinae-2-derived peptides and class II HLA molecules recognized by T cells from atopic individuals. Int Arch Allergy Immunol　114：354-360, 1997

10) Lombardero M, Heymann PW, Platts-Mills TA, et al：Conformational stability of B cell epitopes on group I and group II Dermatophagoides spp. allergens. Effect of thermal and chemical denaturation on the binding of murine IgG and human IgE antibodies. J Immunol　144：1353-1360, 1990

11) Collins SP, Ball G, Vonarx E, et al：Absence of continuous epitopes in the house dust mite major allergens Der p I from Dermatophagoides pteronyssinus and Der f I from Dermatophagoides farinae. Clin Exp Allergy　26：36-42, 1996

12) Takai T, Yokota T, Yasue M, et al：Engineering of the major house dust mite allergen Der f 2 for allergen-specific immunotherapy. Nature Biotechnol　15：754-758, 1997

13) van’t Hof W, Driedijk PC, van den Berg M, et al：Epitope mapping of the Dermatophagoides pteronyssinus house dust mite major allergen Der p II using overlapping synthetic peptides. Mol Immunol　28：1225-1232, 1991

14) Iwamoto N, Nishiyama C, Yasuhara T, et al：Direct expression of Der f 2, a major house dust mite allergen, in Escherichia coli. Int Arch Allergy Immunol　109：356-361, 1996

15) Takai T, Takaoka M, Yasueda H, et al：Dilution-method to refold bacterially expressed recombinant Der f 2 and Der p 2 to exhibit the secondary structure and histamine-releasing activity of natural allergens. Int Arch Allergy Immunol　137：1-8, 2005

16) Nishiyama C, Fukada M, Usui Y, et al：Analysis of the IgE-epitope of Der f 2, a major mite allergen, by in vitro mutagenesis. Mol Immunol　32：1021-1029, 1995

17) Nishiyama C, Hatanaka H, Ichikawa S, et al：Analysis of human IgE epitope of Der f 2 with anti-Der f 2 mouse monoclonal antibodies. Mol Immunol　36：53-60, 1999

18) Nakazawa T, Takai T, Hatanaka H, et al：Multiple-mutation at a potential ligand-binding region decreased allergenicity of a mite allergen Der f 2 without disrupting global structure. FEBS Lett 579：1988-1994, 2005

19) Shoji H, Hanawa M, Shibuya I, et al：Production of recombinant mite allergen Der f I in insect cells and characterization of products―removal of pro-sequence is essential to IgE-binding activity. Biosci Biotechnol Biochem　60：621-625, 1996

20) Yasuhara T, Takai T, Yuuki T, et al：Biologically active recombinant forms of a major house dust mite group 1 allergen Der f 1 with full activities of both cysteine protease and IgE binding. Clin Exp Allergy　31：116-124, 2001

21) Takahashi K, Takai T, Yasuhara T, et al：Production of enzymatically and immunologically active Der f 1 in Escherichia coli. Int Arch Allergy Immunol　122：108-114, 2000

22) Takai T, Mineki R, Nakazawa T, et al：Maturation of the activities of recombinant mite allergens Der p 1 and Der f 1, and its implication in the blockade of proteolytic activity. FEBS Lett　531：265-272, 2002

23) Takai T, Kato T, Yasueda H, et al：Analysis of the structure and allergenicity of recombinant pro-and mature Der p 1 and Der f 1：Major conformational IgE-epitopes blocked by prodomains. J Allergy Clin Immunol　115：555-563, 2005

24) Aas K：What makes an allergen an allergen. Allergy　33：3-14, 1978

25) 市川さおり，畠中秀樹：アレルゲン蛋白質の立体構造．日本女子大学紀要　理学部第9号：1-9, 2001

26) Shakib F, Schulz O, Sewell H：A mite subversive：cleavage of CD23 and CD25 by Der p 1 enhances allergenicity. Immunol Today　19：313-316, 1998

27) Gough L, Schulz O, Sewell HF, et al：The cysteine protease activity of the major dust mite allergen Der p 1 selectively enhances the immunoglobulin E antibody response. J Exp Med　190：1897-1902, 1999

28) Wan H, Winton HL, Soeller C, et al：Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions. J Clin Invest　104：123-133, 1999.

29) Asokananthan N, Graham PT, Stewart DJ, et al：House dust mite allergens induce proinflammatory cytokines from respiratory epithelial cells：the cysteine protease allergen, Der p 1, activates protease-activated receptor (PAR)-2 and inactivates PAR-1. J Immunol　169：4572-4578, 2002

30) Takai T, Kato T, Ota M, et al：Recombinant Der p 1 and Der f 1 with in vitro enzymatic activity to cleave human CD23, CD25, and 1-antitrypsin, and in vivo IgE-eliciting acclivity in mice. Int Arch Allergy Immunol　137：194-200, 2005

31) Sakata Y, Arima K, Takai T, et al：The squamous cell carcinoma antigen 2 inhibits the cysteine proteinase activity of a major mite allergen, Der p 1. J Biol Chem　279：5081-5087, 2004

32) Kato T, Takai T, Mitsuishi K, et al：Cystatin A inhibits IL-8 production by keratinocytes stimulated with Der p 1 and Der f 1：Biochemical skin-barrier against mite cysteine proteases. J Allergy Clin Immunol (in press)

33) Inohara N, Nunez G：ML-a conserved domain involved in innate immunity and lipid metabolism. Trends Biochem Sci　27：219-221, 2002

34) Ichikawa S, Takai T, Inoue T, et al：NMR study on the major mite allergen Der f 2：Its refined tertiary structure, epitopes for monoclonal antibodies and characteristics shared by ML protein group members. J Biochem　137：255-263, 2005

35) Takai T, Kato T, Sakata Y, et al：Recombinant Der p 1 and Der f 1 exhibit cysteine protease activity but no serine protease activity. Biochem Biophys Res Commun　328：944-952, 2005

36) 高井敏朗：アレルゲン・エンジニアリング―アレルゲンの構造・機能とアレルギー・ネットワークの理解を基盤とした次世代の治療戦略．臨床免疫　38：298-305, 2002