MassIVE MSV000080779

Imported Reanalysis Dataset Public PXD002678

Gluten-specific antibodies of celiac disease gut plasma cells recognize long proteolytic fragments that typically harbor T-cell epitopes

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Description

This study aimed to identify proteolytic fragments of gluten proteins recognized by recombinant IgG1 monoclonal antibodies generated from single IgA plasma cells of celiac disease lesions. Peptides bound by monoclonal antibodies in complex gut-enzyme digests of gluten treated with the deamidating enzyme transglutaminase 2, were identified by mass spectrometry after antibody pull-down with protein G beads. The antibody bound peptides were long deamidated peptide fragments that contained the substrate recognition sequence of transglutaminase 2. Characteristically, the fragments contained epitopes with the sequence QPEQPFP and variants thereof in multiple copies, and they typically also harbored many different gluten T-cell epitopes. In the pull-down setting where antibodies were immobilized on a solid phase, peptide fragments with multivalent display of epitopes were targeted. This scenario resembles the situation of the B-cell receptor on the surface of B cells. Conceivably, B cells of celiac disease patients select gluten epitopes that are repeated multiple times in long peptide fragments generated by gut digestive enzymes. As the fragments also contain many different T-cell epitopes, this will lead to generation of strong antibody responses by effective presentation of several distinct T-cell epitopes and establishment of T-cell help to B cells. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Celiac disease ; gliadin ; monoclonal antibodies ; epitopes ; LC-MSMS

Contact

Principal Investigators:
(in alphabetical order) 		Gustavo A. de Souza, 1. Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital - Rikshospitalet, 0424 Oslo, Norway 2. Proteomics Core Facility, Oslo University Hospital-Rikshospitalet, 0424 Oslo, Norway, N/A
Submitting User: ccms

Publications

Dørum S, Steinsbø Ø, Bergseng E, Arntzen MØ, de Souza GA, Sollid LM.
Gluten-specific antibodies of celiac disease gut plasma cells recognize long proteolytic fragments that typically harbor T-cell epitopes.
Sci Rep. Epub 2016 May 5.

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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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