Transcriptional frameshifts contribute to protein allergenicity
| Autor: | Christelle Richard, Julie Tomasina, Claude Favrot, Thierry Olivry, Benoit Hilselberger, Gisèle Kanny, Christine Delebarre-Sauvage, Martine Morisset, F. Codreanu-Morel, Sandrine Jacquenet, O. Roitel, Bernard Bihain, Benoit Thouvenot, E. Beaudouin |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification biology fungi food and beverages RNA Peptide General Medicine medicine.disease_cause Epitope law.invention 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Allergen chemistry Immunoglobulin class switching Biochemistry law Transcription (biology) 030220 oncology & carcinogenesis biology.protein medicine Recombinant DNA Antibody |
| Zdroj: | Journal of Clinical Investigation. 130:5477-5492 |
| ISSN: | 1558-8238 0021-9738 |
| DOI: | 10.1172/jci126275 |
| Popis: | Transcription infidelity (TI) is a mechanism that increases RNA and protein diversity. We found that single-base omissions (i.e., gaps) occurred at significantly higher rates in the RNA of highly allergenic legumes. Transcripts from peanut, soybean, sesame, and mite allergens contained a higher density of gaps than those of nonallergens. Allergen transcripts translate into proteins with a cationic carboxy terminus depleted in hydrophobic residues. In mice, recombinant TI variants of the peanut allergen Ara h 2, but not the canonical allergen itself, induced, without adjuvant, the production of anaphylactogenic specific IgE (sIgE), binding to linear epitopes on both canonical and TI segments of the TI variants. The removal of cationic proteins from bovine lactoserum markedly reduced its capacity to induce sIgE. In peanut-allergic children, the sIgE reactivity was directed toward both canonical and TI segments of Ara h 2 variants. We discovered 2 peanut allergens, which we believe to be previously unreported, because of their RNA-DNA divergence gap patterns and TI peptide amino acid composition. Finally, we showed that the sIgE of children with IgE-negative milk allergy targeted cationic proteins in lactoserum. We propose that it is not the canonical allergens, but their TI variants, that initiate sIgE isotype switching, while both canonical and TI variants elicit clinical allergic reactions. |
| Databáze: | OpenAIRE |
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