Structural insights into the IgE mediated responses induced by the allergens Hev b 8 and Zea m 12 in their dimeric forms


Por: Mares-Mejiá I., Martínez-Caballero S., Garay-Canales C., Cano-Sánchez P., Torres-Larios A., Lara-González S., Ortega E., Rodríguez-Romero A.

Publicada: 2 sep 2016
Categoría: Multidisciplinary

Resumen:
Oligomerization of allergens plays an important role in IgE-mediated reactions, as effective crosslinking of IgE-Fc epsilon RI complexes on the cell membrane is dependent on the number of exposed B-cell epitopes in a single allergen molecule or on the occurrence of identical epitopes in a symmetrical arrangement. Few studies have attempted to experimentally demonstrate the connection between allergen dimerization and the ability to trigger allergic reactions. Here we studied plant allergenic profilins rHev b 8 (rubber tree) and rZea m 12 (maize) because they represent an important example of cross-reactivity in the latex-pollen-food syndrome. Both allergens in their monomeric and dimeric states were isolated and characterized by exclusion chromatography and mass spectrometry and were used in immunological in vitro experiments. Their crystal structures were solved, and for Hev b 8 a disulfide-linked homodimer was found. Comparing the structures we established that the longest loop is relevant for recognition by IgE antibodies, whereas the conserved regions are important for cross-reactivity. We produced a novel monoclonal murine IgE (mAb 2F5), specific for rHev b 8, which was useful to provide evidence that profilin dimerization considerably increases the IgE-mediated degranulation in rat basophilic leukemia cells.

Filiaciones:
Mares-Mejiá I.:
 Instituto de Química, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, 04510, Mexico

Martínez-Caballero S.:
 Instituto de Química, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, 04510, Mexico

Garay-Canales C.:
 Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Cd. Universitaria, Coyoacán, Ciudad de México, 04510, Mexico

Cano-Sánchez P.:
 Instituto de Química, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, 04510, Mexico

Torres-Larios A.:
 Instituto de Fisiologiá Celular, Universidad Nacional Autónoma de México, Cd. Universitaria, Coyoacán, Ciudad de México, 04510, Mexico

Lara-González S.:
 Instituto Potosino de Investigación Científica y Tecnológica, Camino a la Presa San José 2055, San Luis Potosí, 78216, Mexico

Ortega E.:
 Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Cd. Universitaria, Coyoacán, Ciudad de México, 04510, Mexico

Rodríguez-Romero A.:
 Instituto de Química, Universidad Nacional Autónoma de México, Coyoacán, Ciudad de México, 04510, Mexico
ISSN: 20452322
Editorial
NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 6 Número:
Páginas:
WOS Id: 000382375600002
ID de PubMed: 27586352
imagen All Open Access, Gold

MÉTRICAS