Vacuolar Serine Protease Is a Major Allergen of Fusarium proliferatum and an IgE-Cross Reactive Pan-Fungal Allergen

다국어 초록 (Multilingual Abstract)

Purpose: Fusarium species are among prevalent airborne fungi and causative agents of human respiratory atopic disorders. We previously identified a 36.5-kDa F. proliferatum component recognized by IgE antibodies in 9 (53%) of the 17 F. proliferatum-sensitized atopic serum samples. The purpose of this study is to characterize the 36.5-kDa allergen of F. proliferatum. Methods: Characterization of allergens and determination of IgE cross-reactivity were performed by cDNA cloning/expression and immunoblot inhibition studies. Results: Based on the finding that the 36.5-kDa IgE-binding component reacted with the mouse monoclonal antibody FUM20 against fungal vacuolar serine protease allergens, the cDNA of F. proliferatum vacuolar serine protease (Fus p 9.0101) was subsequently cloned. Nine serum samples from respiratory atopic patients with IgE binding to the vacuolar serine protease allergen of Penicillium chrysogenum (Pen ch 18) also showed IgE-immunoblot reactivity to rFus p 9.0101. The purified rFus p 9.0101 can inhibit IgE and FUM20 binding to the 36.5-kDa component of F. proliferatum. Thus, a novel and important Fus p 9.0101 was identified. The rPen ch 18 can inhibit IgE binding to Fus p 9.0101. It indicates that IgE cross-reactivity between Fus p 9.0101 and Pen ch 18 also exists. Furthermore, neither rFus p 9.0101 K88A nor rPen ch 18 K89A mutants inhibited IgE binding to rFus p 9.0101. Lys88 was considered a critical core amino acid in IgE binding to r Fus p 9.0101 and a residue responsible for IgE cross-reactivity between Fus p 9.0101 and Pen ch 18 allergens. Conclusions: Results obtained from this study indicate that vacuolar serine protease may be a major allergen of F. proliferatum and an important IgE cross-reactive pan-fungal allergen, and provide important bases for clinical diagnosis of fungal allergy.

참고문헌 (Reference)

1 Chou H, "cDNA cloning, biological and immunological characterization of the alkaline serine protease major allergen from Penicillium chrysogenum" 127 : 15-26, 2002

2 Shen HD, "cDNA cloning and immunologic characterization of Pen o 18, the vacuolar serine protease major allergen of Penicillium oxalicum" 137 : 115-124, 2001

3 Chou H, "Vacuolar serine protease is a major allergen of Cladosporium cladosporioides" 146 : 277-286, 2008

4 Chou H, "The transaldolase, a novel allergen of Fusarium proliferatum, demonstrates IgE cross-reactivity with its human analogue" 9 : e103488-, 2014

5 Shen HD, "The importance of serine proteinases as aeroallergens associated with asthma" 119 : 259-264, 1999

6 Prince HE, "Skin reaction patterns to dematiaceous mold allergens" 29 : 535-538, 1971

7 Tripathi P, "Serine protease activity of Cur l 1 from Curvularia lunata augments Th2 response in mice" 29 : 292-302, 2009

8 Moehle CM, "Protease B of the lysosomelike vacuole of the yeast Saccharomyces cerevisiae is homologous to the subtilisin family of serine proteases" 7 : 4390-4399, 1987

9 Lin WL, "Production and characterization of monoclonal antibodies to serine proteinase allergens in Penicillium and Aspergillus species" 30 : 1653-1662, 2000

10 Tai HY, "Pen ch 13 major fungal allergen decreases CD44 expression in human bronchial epithelial cells" 153 : 367-371, 2010

11 Tai HY, "Pen ch 13 allergen induces secretion of mediators and degradation of occludin protein of human lung epithelial cells" 61 : 382-388, 2006

12 Shen HD, "Molecular and immunological characterization of Pen ch 18, the vacuolar serine protease major allergen of Penicillium chrysogenum" 58 : 993-1002, 2003

13 Rudolf Valenta, "Mold Allergens in Respiratory Allergy: From Structure to Therapy" 대한천식알레르기학회 7 (7): 205-220, 2015

14 Esch RE, "Manufacturing and standardizing fungal allergen products" 113 : 210-215, 2004

15 Cheng TT, "Lys89, Lys90, and Phe91 are critical core amino acid residues of the Pen ch 18 major fungal allergen recognized by human IgE antibodies" 375 : 671-674, 2008

16 Sharpe RA, "Indoor fungal diversity and asthma: a meta-analysis and systematic review of risk factors" 135 : 110-122, 2015

17 Shen HD, "Identification of vacuolar serine proteinase as a major allergen of Aspergillus fumigatus by immunoblotting and N-terminal amino acid sequence analysis" 31 : 295-302, 2001

18 Gupta R, "Identification of serine protease as a major allergen of Curvularia lunata" 59 : 421-427, 2004

19 정경용, "Current Status of Standardization of Inhalant Allergen Extracts in Korea" 대한천식알레르기학회 6 (6): 196-200, 2014

20 Sams JT, "Cross-antigenicity of common mold antigens" 26 : 55-60, 1968

21 Frederick GD, "Cloning and characterisation of pepC, a gene encoding a serine protease from Aspergillus niger" 125 : 57-64, 1993

22 Shen HD, "Characterization of the house dust mite allergen Der p 7 by monoclonal antibodies" 25 : 416-422, 1995

23 Namvar S, "Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model" 45 : 982-993, 2015

24 Shen HD, "Aspergillus and Penicillium allergens:focus on proteases" 7 : 351-356, 2007

25 Kurup VP, "Alkaline serine proteinase from Aspergillus fumigatus has synergistic effects on Asp-f-2-induced immune response in mice" 129 : 129-137, 2002

26 Nebes VL, "Activation of the proteinase B precursor of the yeast Saccharomyces cerevisiae by autocatalysis and by an internal sequence" 266 : 22851-22857, 1991

27 Chou H, "A vacuolar serine protease (Rho m 2) is a major allergen of Rhodotorula mucilaginosa and belongs to a class of highly conserved pan-fungal allergens" 138 : 134-141, 2005