3167 Protein-protein interactions determine IgE reactivity to polygalacturonase from Cupressus sempervirens pollen

Tuesday, 6 December 2011: 13:45 - 14:00
Gran Cancún 2 (Cancún Center)

Youcef Shahali , UMR 7195 LSABM, ESPCI-ParisTech, Paris, France

Jean-Pierre Sutra, PhD , UMR 7195 LSABM, ESPCI-ParisTech, Paris, France

Sylvie Chollet-Martin , Unity of Immunology Autoimmunity and Hypersensibility, Bichat Hospital, Paris, France

Iman Haddad , USR 3149 SMBP, ESPCI-ParisTech, Paris, France

Joëlle Vinh, PhD , USR 3149 SMBP, ESPCI-ParisTech, Paris, France

Adriano Mari, MD , CMA, Rome, Italy

Denis Charpin , Hopital Nord de Marseille, Marseille , France

Hélène Sénéchal, PhD , CSS 5, INSERM, Paris, France

Pascal Poncet, PhD , Infection and Epidemiology, Institut Pasteur, Paris, France

Background: In a recent proteomic study, we identified in Italian cypress (Cupressus sempervirens, Cups) pollen grains, two proteins at 43 and 60 kDa, homologous to already known Cupressaceae polygalacturonase (PG) proteins. The 60-kDa PG is suspected to be a multi-protein complex including the 43-kDa PG and one or more proteins with lectin-like properties

Objective: In the present study, cypress pollen PGs were further characterized and the molecular basis of their allergenicity including the presence of specific IgE directed against cross-reactive carbohydrate determinants (CCDs) were investigated.

Methods: Cups pollen PBS extracts were characterized using two- and double one-dimensional electrophoresis followed by IgE immunoblotting. The IgE reactivity to carbohydrate- vs peptide-specific determinants was investigated using both bromelain inhibition and Con A-binding assays. Pollen proteins were also prefractionated in their native forms using size exclusion chromatography. The presence of multi-protein complexes were investigated by using 2-D blue native (BN)-PAGE/ SDS-PAGE electrophoresis.

Results: Upon bromelain inhibition assay, we revealed that 70% of tested patients displayed CCD-specific IgE to the 43-kDa PG while its isoenzyme of 60 kDa appeared to be exclusively recognized for its peptide-specific determinants. The specific binding of the Con A lectin to the 43-kDa PG, and not to the 60-kDa isoenzyme, demonstrated the presence of exposed mannose-containing oligosaccharides only on the 43-kDa protein. This fact reflects fundamental differences between specific IgE-binding epitopes involved in the recognition of the 43-kDa and 60-kDa proteins making these two cypress pollen PGs immunologically distinguishable. The present results suggest that in the 60-kDa protein complex, the CCDs of the 43-kDa PG are not exposed due to the binding of a lectin-like protein exhibiting peptidic IgE reactive epitopes recognized by 25% of tested patients.

Conclusion: The current study demonstrates that the sensitization to the Cups pollen PG is mainly due to CCD bromelain-type epitopes and directly associated with an increased prevalence of IgE reactivity to cypress pollen extracts due to CCD interference. However, the Cups pollen PG and its carbohydrate-specific determinants seem to play a key role in the dynamics of protein-protein interaction in cypress pollen and may confer to protein complexes a higher allergenicity.