Cryptic antigenic determinants on the extracellular pyruvate dehydrogenase complex/mimeotope found in primary biliary cirrhosis. A probe by affinity mass spectrometry.

The Journal of Biological Chemistry
T T YipT W Hutchens

Abstract

Affinity mass spectrometry (AMS) was used to evaluate the structural diversity of the E2 component of pyruvate dehydrogenase complex (PDC) in normal and diseased liver cells, including those from patients with the autoimmune disease primary biliary cirrhosis (PBC). Two different antibodies to PDC-E2, the immunodominant mitochondrial autoantigen in patients with PBC, were used. AMS was performed directly on frozen liver sections and purified bile duct epithelial cells. Mass spectrometric signals associated with the molecular recognition of PBC-specific antigenic determinants were enhanced by an in situ enzyme-linked signal amplification process. Samples from patients with PBC gave strong positive signals for the antigen(s) recognized by the monoclonal antibody C355.1. Conversely, tissues from normal and disease controls showed only a minimal signal. AMS was used to identify specific antigenic determinants within the E2 component of PDC for comparison with unknown antigenic determinants observed by affinity capture with C355.1 monoclonal antibody from PBC samples. PDC components bound to C355.1 were mapped and identified by mass before dissociation from the E2 component. A similar approach was used to identify unknown antigenic d...Continue Reading

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Citations

Aug 15, 1998·Mass Spectrometry Reviews·R W Nelson
Mar 21, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A MattaliaM E Gershwin
Dec 24, 1997·Clinical Immunology and Immunopathology·J Van de WaterM E Gershwin
Mar 31, 2004·Plant Physiology and Biochemistry : PPB·Jorge E CamposAlejandro Blanco-Labra
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Sep 7, 2012·Analytical Chemistry·Ashraf G MadianFred E Regnier
Aug 30, 2008·Molecular & Cellular Proteomics : MCP·Junmei ZhangYingming Zhao
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Dec 22, 2006·Expert Review of Proteomics·Dobrin Nedelkov
Nov 2, 2013·World Journal of Hepatology·Ourania SfakianakiElias Kouroumalis

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