Our data indicate that -- on the level of TH lymphocytes -- SIT induces tolerance to the allergen and a modulation of the cytokine pattern produced in response to allergen stimulation.
Twenty-five T cell clones specific for Bet v I were established from the peripheral blood of two birch pollen-allergic patients. The T cell epitopes of these clones were mapped using dodecapeptides overlapping for 2 amino acids (neighbors share 10 residues) spanning the whole amino acid sequence of the protein (159 amino acids). In total, 7 epitopes could be detected. One donor displayed 6 distinct T cell specificities for the Bet v I molecule in 14 T cell clones; for the other donor, 4 stimulating peptides for 11 clones could be identified. Two T cell epitopes were recognized by both subjects. One of these might represent an immunodominant epitope located at amino acid position 77-92 of the Bet v I molecule, as in 13/25 T cell clones activation could be induced by this amino acid sequence. One T cell clone reacted with purified pollen-derived Bet v I, but neither with any peptide synthesized according to a Bet v I-encoding cDNA nor with the respective recombinant protein. Upon stimulation with allergen, the majority of the clones (21/24) revealed the TH0 or TH2 type of cytokine production (interleukin-4 production), indicating their importance in the pathogenesis of the allergic disease.
Purified preparations of allergenic proteins from plants, and in particular from pollens, consist of multiple closely related isoforms. These isoforms are highly similar in their amino acid sequences, yet they display different properties with respect to antibody binding. In this study we report of differential potencies of cross-reacting tree pollen allergens and cloned isoforms of these allergens to activate allergen-specific T-lymphocyte clones (T-cell clones ; TCC). Six TCC with specifity for Bet v 1, a representative tree pollen major allergen, were established from peripheral blood of five birch-pollen-allergic donors. All TCC displayed the helper-cell phenotype. Five TCC reacted with distinct epitopes present on natural (n) and on recombinant (r) Bet v 1. One TCC could not be stimulated with r Bet v 1, in spite of strong reactivity with purified natural Bet v 1. The TCC were tested in proliferation assays using purified n Bet v 1, n Cor a 1 (the homologous major allergen of hazel pollen), r Bet v 1, four recombinant isoforms of Cor a 1 and peptides representing corresponding T-cell stimulating regions (isoepitopes) on these proteins. The clones showed different patterns of reactivity in response to stimulation with the five recombinant molecules and the corresponding peptides. Certain exchanges of amino acids within stimulating peptides correlated with a lack of proliferation of the TCC tested. These findings are important with respect to the use of broadly cross-reactive recombinant allergens or allergen-derived peptides for immunotherapy of type I allergy.Type I allergy to tree pollens is very common in the northern hemisphere. In this respect, pollens from trees of the order Fagales, in particular birch, hazel and alder, represent the most important sources of allergens [l, 21. The major allergens of these pollens (Bet v 1, Cor a 1 and A h g 1) show a high degree of similiarity at the nucleic acid 131 and at the amino acid levels [4], and cross-reactivity was described for IgE antibodies [5] and for T-cell clones (TCC) [6]. This fits well with the observation that tree pollen-allergic patients develop symptoms when exposed to pollens from all these tree species.Natural allergens consist of multiple isoallergens [7 -91. Recently, four isoforms of Cor a 1, the major allergen of hazel pollen, were cloned, sequenced and expressed as recombinant non-fusion proteins [8]. Comparison of the amino acid sequences of these Cor a 1 isoforms revealed identities Correspondence to
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