Responses of human birch pollen allergen-reactive T cells to chemically modified allergens (allergoids).
BACKGROUND
Allergoids are widely used in specific immunotherapy for the treatment of IgE-mediated allergic diseases.


OBJECTIVE
The aim of this study was to analyse whether a modification of birch pollen allergens with formaldehyde affects the availability of T-cell epitopes.


METHODS
Efficient modification of the allergens was verified by determining IgE and IgG binding activity using ELISA inhibition tests. T-cell responses to birch pollen allergoids were analysed in polyclonal systems, using peripheral blood mononuclear cells (PBMC) of five birch pollen-allergic individuals, as well as birch pollen extract-reactive T-cell lines (TCL), established from the peripheral blood of 14 birch pollen-allergic donors. To determine whether the modification of natural (n)Bet v 1 with formaldehyde or maleic anhydride results in epitope-specific changes in T-cell reactivities, 22 Bet v 1-specific T-cell clones (TCC), established from nine additional birch pollen-allergic individuals, were tested for their reactivity with these products.


RESULTS
The majority of PBMC and TCL showed a reduced response to the birch pollen extract allergoid. Bet v 1-specific TCC could be divided into allergoid-reactive and -non-reactive TCC. No simple correlation between possible modification sites of formaldehyde in the respective T-cell epitopes and the stimulatory potential of the allergoid was observed. Mechanisms of suppression or of anergy induction were excluded as an explanation for the non-reactivity of representative TCC. All TCC could be stimulated by maleylated and unmodified nBet v 1 to a similar extent.


CONCLUSIONS
These results demonstrate differences in the availability of T-cell epitopes between allergoids and unmodified allergens, which are most likely due to structural changes within the allergen molecule.
Dormann
D
D
Clinical Research Unit, Department of Dermatology, University of Mainz, Mainz, Germany.
Ebner
C
C
Jarman
E R
ER
Montermann
E
E
Kraft
D
D
Reske-Kunz
A B
AB
D000485:Allergens / Q000494:pharmacology*; D000080384:Allergoids; D000595:Amino Acid Sequence; D052179:Antigens, Plant; D005557:Formaldehyde / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D010936:Plant Extracts / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D011058:Pollen / Q000009:adverse effects / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D000485:Allergens; D000080384:Allergoids; D052179:Antigens, Plant; D010936:Plant Extracts; D010940:Plant Proteins; C061312:Bet v 1 allergen, Betula; D005557:Formaldehyde