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Mapping of T‐cell epitopes of Phl p 5: evidence for crossreacting and non‐crossreacting T‐cell epitopes within Phl p 5 isoallergens
Author(s) -
Müller Wd,
Theodor Karamfilov,
Helga Kahlert,
Stüwe Ht,
B Fahlbusch,
Oliver Cromwell,
Helmut Fiebig,
Lothar Jäger
Publication year - 1998
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1046/j.1365-2222.1998.00432.x
Subject(s) - epitope , immunology , biology , t cell , allergen , epitope mapping , recombinant dna , antigen , microbiology and biotechnology , immune system , allergy , gene , genetics
Background Group 5 allergens represent major grass pollen allergens because of their high sensitization indices. The identification of T‐cell epitopes of these allergens is a prerequisite for the design of immunotherapeutic strategies based on peptide vaccination or modified allergens with conserved T‐cell epitopes. Objective This study was undertaken to determine T‐cell epitopes on Phl p 5 major pollen allergen of timothy grass ( Phleum pratense ). Methods T‐cell lines (TCLs) and T‐cell clones (TCCs), specific to Phl p 5, were established from the peripheral blood of 18 patients allergic to grass pollen. All TCCs were mapped for epitope specificities using 178 overlapping dodecapeptides representing the primary structures of two isoforms of Phl p 5 (Phl p 5a and Phl p 5b). Phenotype and cytokine production profiles of TCCs were tested. Selected TCCs were analysed for HLA class II restriction. Results A total of 82 TCCs were isolated. All TCCs displayed the helper cell (TH) phenotype. Their reactivity with two recombinant expressed isoforms of Phl p 5a and Phl p 5b was heterogeneous. The epitope specificity of the TCCs was then revealed. Nineteen T‐cell epitopes could be identified on Phl p 5. Eighty‐one percent of mapped TCCs recognized three T‐cell reactive regions on the Phl p 5 allergen. Some TCCs were reactive with isoepitopes presenting on Phl p 5a as well as Phl p 5b. Allergen‐specific stimulation induced a TH 0 ‐like type of cytokine production in 25 of 50 TCCs. Almost all TCCs secreted high concentrations of interleukin‐13. Conclusion Phl p 5, a major grass pollen allergen, contains several T‐cell epitopes. Some epitope regions were recognized by several patients. Epitope recognition pattern could not be correlated with special HLA class II haplotypes. T‐cell stimulating isoepitopes were found at corresponding regions of Phl p 5a and Phl p 5b isoforms.