Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments: candidates for a novel form of specific immunotherapy.
A novel approach to reduce the anaphylactic activity of allergens is suggested. The strategy makes use of the presence of conformational immunoglobulin E (IgE) epitopes on one of the most common allergens. The three dimensional structure of the major birch pollen allergen, Bet v 1, was disrupted by expressing two parts of the Bet v 1 cDNA representing amino acids 1-74 and 75-160 in Escherichia coli. In contrast to the complete recombinant Bet v 1, the fragments showed almost no allergenicity and exhibited random coil conformation as analyzed by circular dichroism. Both nonanaphylactic fragments induced proliferation of human Bet v 1-specific T cell clones, indicating that they harbored all dominant T cell epitopes and therefore may be considered as a basis for the development of a safe and specific T cell immunotherapy.
Vrtala
S
S
Department of Immunopathology, Institute of General and Experimental Pathology, AKH, University of Vienna, Austria.
Hirtenlehner
K
K
Vangelista
L
L
Pastore
A
A
Eichler
H G
HG
Sperr
W R
WR
Valent
P
P
Ebner
C
C
Kraft
D
D
Valenta
R
R
D000485:Allergens; D000707:Anaphylaxis / Q000517:prevention & control; D000818:Animals; D052179:Antigens, Plant; D002942:Circular Dichroism; D000939:Epitopes; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000628:therapy*; D007073:Immunoglobulin E / Q000378:metabolism; D007167:Immunotherapy; D051379:Mice; D010446:Peptide Fragments / Q000276:immunology*; D010940:Plant Proteins / Q000737:chemistry* / Q000276:immunology / Q000302:isolation & purification; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology*
D000485:Allergens; D052179:Antigens, Plant; D000939:Epitopes; D010446:Peptide Fragments; D010940:Plant Proteins; D011994:Recombinant Proteins; C061312:Bet v 1 allergen, Betula; D007073:Immunoglobulin E