Unlocking the allergenic structure of the major house dust mite allergen der f 2 by elimination of key intramolecular interactions.
We report on the structural background of the remarkable reduction of allergenicity in engineering of the major house dust mite allergen Der f 2. Disruption of intramolecular disulfide bonds in Der f 2 caused extensive conformational change that was monitored by circular dichroism and gel-filtration analysis. The degree of conformational change correlated well with the degree of reductions in the capacity to bind IgE and to induce histamine release from basophils in mite-allergic patients. Loosening the rigid tertiary structure by elimination of key intramolecular interactions is an effective strategy to reduce the number of high affinity IgE epitopes of allergen vaccine.
Takai
T
T
Bioscience Research and Development Laboratory, Asahi Breweries, Ltd; Ibaraki, Japan. toshiro.takai@asahibeer.co.jp
Ichikawa
S
S
Yokota
T
T
Hatanaka
H
H
Inagaki
F
F
Okumura
Y
Y
D000818:Animals; D000915:Antibody Affinity; D039741:Antigens, Dermatophagoides; D001491:Basophils / Q000187:drug effects / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D008925:Mites / Q000737:chemistry*; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D039741:Antigens, Dermatophagoides; D004220:Disulfides; D006023:Glycoproteins; D007073:Immunoglobulin E; D006632:Histamine