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The rise and fall of IgE

Vernersson, Molly, 1967- (författare)
Uppsala universitet, Institutionen för cell- och molekylärbiologi
Uppsala universitet Teknisk-naturvetenskapliga vetenskapsområdet. Biologiska sektionen. Institutionen för cell- och molekylärbiologi. (creator_code:org_t)
ISBN 91-554-5388-0
Uppsala : Acta Universitatis Upsaliensis, 2002
Engelska 61 s.
Serie: Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, 1104-232X ; 742
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  • Doktorsavhandling (övrigt vetenskapligt)
Abstract Ämnesord
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  • Immunoglobulin E (IgE) occurs exclusively in mammals and is one of five immunoglobulin (Ig) classes found in man. Unlike other isotypes, IgE is best known for its pathological effects, whereas its physiological role remains somewhat elusive. To trace the emergence of IgE and other post-switch isotypes we have studied Ig expression in two monotreme species, the duck-billed platypus (Ornithorhynchus anatinus) and the short-beaked echidna (Tachyglossus aculeatus), leading to the cloning of IgE, two IgG isotypes in platypus and echidna IgE. The presence of IgE and the conservation of the overall structure in all extant mammalian lineages indicates an early appearance in mammalian evolution and a selective advantage of structural maintenance. Furthermore, both of the two highly divergent platypus γ-chains have three constant domains. Hence, the major evolutionary changes that gave rise to the IgE and IgG isotypes of present day mammals occurred before the separation of monotremes from the marsupial and placental lineages, estimated to have occurred 150-170 million years ago.As the central mediator in atopic allergy, IgE is a prime target in the development of preventive treatments. This thesis describes an active immunization strategy that has the potential to reduce IgE to a clinically significant extent. The active vaccine component is a chimeric IgE molecule, Cε2-Cε3-Cε4. The receptor-binding target domain, Cε3, is derived from the recipient species, whereas the flanking domains, acting both as structural support and to break T-cell tolerance, are derived from an evolutionarily distant mammal. Vaccination of ovalbumin-sensitized rats resulted in a substantial reduction in total IgE in three out of four strains, accompanied by a significant reduction in skin-reactivity upon allergen challenge. No cross-linking activity was observed and the response to vaccination was reversible with time. The apparent safety and efficacy of the vaccine suggest that active immunization against IgE has the potential to become a therapeutic method for humans. Furthermore, the cloning and expression of the pig (Sus scrufa) ε-chain will facilitate the development of sensitive and specific assays for pig IgE, thus increasing the possibilities of using the pig model in future studies of IgE-mediated reactions.

Ämnesord

NATURVETENSKAP  -- Biologiska vetenskaper -- Biokemi och molekylärbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

Nyckelord

Cell and molecular biology
Immunoglobulin
IgE
evolution
atopic allergy
vaccine
Cell- och molekylärbiologi
NATURAL SCIENCES Biology Cell and molecular biology
NATURVETENSKAP Biologi Cell- och molekylärbiologi
molekylär immunologi
Molecular Immunology

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