Dissection of the IgE and T-cell recognition of the major group 5 grass pollen allergen Phl p 5.

Abstract

BACKGROUND:

The major timothy grass pollen allergen Phl p 5 belongs to the most potent allergens involved in hay fever and asthma.

OBJECTIVE:

This study characterized immune-dominant IgE- and T-cell-recognition sites of Phl p 5.

METHODS:

Seven peptides, P1 to P7 with a length of 31 to 38 amino acids that spanned the Phl p 5 sequence, were synthesized, characterized by circular dichroism spectroscopy, and tested for IgE reactivity, basophil activation, and T-cell reactivity. Carrier-bound peptides were studied for their ability to induce IgG antibodies in rabbits which recognize Phl p 5 or cross-reactive allergens from different grass species. Peptide-specific antibodies were tested for the capability to inhibit IgE reactivity to Phl p 5 and allergen-induced basophil activation of patients with allergy.

RESULTS:

The peptides exhibited no secondary structure and showed no IgE reactivity or relevant allergenic activity, indicating that Phl p 5 IgE epitopes are conformational. Except for P3, peptide-specific IgG antibodies blocked IgE binding to Phl p 5 of patients with allergy and cross-reacted with temperate grasses. IgE inhibition experiments and molecular modeling identified several clustered conformational IgE epitopes on the N- as well as C-terminal domain of Phl p 5. P4, which stimulated the strongest T-cell and cytokine responses in patients, was not part of the major IgE-reactive regions.

CONCLUSION:

Our study shows an interesting dissociation of the major IgE- and T-cell-reactive domains in Phl p 5 which provides a basis for the development of novel forms of immunotherapy that selectively target IgE or T-cell responses.

• Authors: Margarete Focke-Tejkl, Raffaela Campana, Renate Reininger, Christian Lupinek, Katharina Blatt, Peter Valent, Tea Pavkov-Keller, Walter Keller, Rudolf Valenta
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 133 Issue 3 Pg. 836-45.e11 (Mar 2014) ISSN: 1097-6825 [Electronic] United States
• PMID: 24182774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Chemical References

• Cytokines
• Phl p V protein, Phleum pratense
• Plant Proteins
• Immunoglobulin E

Topics

• Adolescent
• Adult
• Amino Acid Sequence
• Animals
• Basophils (physiology)
• Child
• Cross Reactions
• Cytokines (biosynthesis)
• Epitope Mapping
• Female
• Humans
• Immunoglobulin E (immunology)
• Lymphocyte Activation
• Male
• Middle Aged
• Models, Molecular
• Molecular Sequence Data
• Plant Proteins (chemistry, immunology)
• Protein Structure, Secondary
• Rabbits
• T-Lymphocytes (immunology)