Identification of isoform-specific T-cell epitopes in the major timothy grass pollen allergen, Phl p 5
Article first published online: 5 APR 2002
Blackwell Science Ltd, Oxford
Clinical & Experimental Allergy
Volume 29, Issue 12, pages 1614–1625, December 1999
How to Cite
Würtzen, P. A., Bufe, A., Wissenbach, M., Madsen, H. O., Ipsen, H., Arnved, J. and Van Neerven, R. J. J. (1999), Identification of isoform-specific T-cell epitopes in the major timothy grass pollen allergen, Phl p 5. Clinical & Experimental Allergy, 29: 1614–1625. doi: 10.1046/j.1365-2222.1999.00652.x
- Issue published online: 5 APR 2002
- Article first published online: 5 APR 2002
- grass group 5 allergens;
- major histocompatibility complex;
- T lymphocytes;
- T-cell epitopes;
- T-cell receptors
The involvement of CD4+ T cells in the pathophysiology of atopic disease is well established.
To gain further insight into the activation requirements for allergen-specific T cells, we characterized epitope specificity, HLA restriction and T-cell receptor (TCR) usage for T cells specific to Phl p 5, the group 5 major allergen of the grass Phleum pratense.
To identify the T-cell epitopes of Phl p 5, three Phl p 5-specific T-cell lines (TCLs) and 15 T-cell clones (TCCs) generated from the peripheral blood of three grass-allergic patients were tested with recombinant truncated Phl p 5a fragments and synthetic Phl p 5b peptides representing these two different recombinant Phl p 5 isoallergens. Additional activation experiments with HLA-subtyped antigen-presenting cells and flow cytometry analysis with TCR V-specific mAb were performed to further characterize the activation requirements for Phl p 5-specific TCCs.
At least nine distinct T-cell specificities were identified and the T-cell epitopes recognized differed considerably among the three patients. Most of the epitopes found were isoform-specific, whereas three epitopes were shared between Phl p 5a and 5b. Several human leucocyte antigen (HLA) class II molecules were involved in the recognition of Phl p 5. Different HLA restriction specificities were even found among TCCs specific to the same epitope region. All TCCs were TCR-α/β positive, and an overrepresentation of TCR Vβ 3.1+ clones among TCCs specific to Phl p 5 appear to exists as 31% (4/13) of the TCCs expressed TCR Vβ 3.1 (compared with 5% TCR Vβ 3.1+ T cells in human peripheral blood) with no correlation with epitope specificity or HLA restriction.
The T-cell reactivity of the three grass-allergic patients investigated shows that isoallergen-specific T-cell epitopes are found throughout the peptide backbone of Phl p 5a and Phl p 5b, and dominant T-cell epitopes of Phl p 5 were not identified. This indicates that a mixture of at least full-length rPhl p 5a and rPhl p 5b may be required to target the total Phl p 5-specific T-cell response of atopic patients.