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Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity

journal contribution
posted on 2004-01-01, 00:00 authored by A Drew, N Eusebius, L Kenins, H de Silva, Cenk SuphiogluCenk Suphioglu, J Rolland, R O'Hehir
Hev b 6.01 is a major allergen of natural rubber latex with sensitization of 70–86% of latex glove-allergic subjects. Recently, we mapped the immunodominant T cell sites of Hev b 6.01 to the highly IgE-reactive hevein (Hev b 6.02) domain. Hev b 6.01 contains 14 cysteine residues with multiple disulphide bridges stabilizing tertiary conformation. With the goal of a standardized specific immunotherapy we developed hypoallergenic Hev b 6.01 mutants by site-directed mutagenesis of selected cysteine residues (3, 12, 17, and 41) within the Hev b 6.02 domain. Peptides corresponding to the Hev b 6.02 domain of two of the mutants were also synthesized. These mutants and peptide variants showed markedly decreased or ablated latex-allergic patient serum IgE binding by immunoblotting and ELISA. Basophil activation testing confirmed markedly decreased activation with successive cysteine substitutions of the mutants and complete abrogation with the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide. Retention of T cell reactivity is crucial for effective specific immunotherapy and all mutants and peptide variants maintained their latex-specific T cell reactivity. The ablated allergenicity but retained T cell reactivity of the Hev b 6.02 (Cys 3, 12, 17, 41 Ala) peptide suggests this peptide is a suitable candidate for inclusion in a latex immunotherapy preparation.

History

Journal

Journal of immunology

Volume

173

Pagination

5872 - 5879

Publisher

American Association of Immunologists

Location

Baltimore, Md.

ISSN

0022-1767

eISSN

1550-6606

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2004, The American Association of Immunologists, Inc.

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