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

Drew, Alexander C., Eusebius, Nirupama P, Kenins, Linda, de Silva, Harini D., Suphioglu, Cenk, Rolland, Jennifer M. and O'Hehir, Robyn E. 2004, Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity, Journal of immunology, vol. 173, pp. 5872-5879.

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Title Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity
Author(s) Drew, Alexander C.
Eusebius, Nirupama P
Kenins, Linda
de Silva, Harini D.
Suphioglu, CenkORCID iD for Suphioglu, Cenk orcid.org/0000-0003-0101-0668
Rolland, Jennifer M.
O'Hehir, Robyn E.
Journal name Journal of immunology
Volume number 173
Start page 5872
End page 5879
Publisher American Association of Immunologists
Place of publication Baltimore, Md.
Publication date 2004
ISSN 0022-1767
Summary 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.
Language eng
Field of Research 039901 Environmental Chemistry (incl Atmospheric Chemistry)
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2004, The American Association of Immunologists, Inc.
Persistent URL http://hdl.handle.net/10536/DRO/DU:30019592

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