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Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis

Leung, PSC and Krams, S and Munoz, S and Surh, CP and Ansari, A and Kenny, T and Robbins, DL and Fung, J and Starzl, TE and Maddrey, W and Coppel, RL and Gershwin, ME (1992) Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis. Journal of Autoimmunity, 5 (6). 703 - 718. ISSN 0896-8411

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Abstract

Further to define the epitopes of PDC-E2, the major autoantigen in primary biliary cirrhosis (PBC), we have developed and characterized five human monoclonal antibodies. These antibodies were derived by fusing a regional hepatic lymph node from a patient with PBC with the mouse human heterohybrid cell line F3B6. Previous studies of epitope mapping of PDC-E2 have relied on whole sera and have suggested that the immunodominant epitope lies within the inner lipoyl domain of the molecule. However, selective absorption studies using whole sera and a series of overlapping recombinant peptides of PDC-E2 have suggested that the epitope may also include a large conformational component. Moreover, several laboratories have suggested that autoantibodies against the 2-oxo acids dehydrogenase autoantigens are cross-reactive. The five monoclonal antibodies generated included three IgG2a and two IgM antibodies and were studied for antigen specificity using recombinant PDC-E2, recombinant BCKD-E2, histone, dsDNA, IgG (Fc), collagen and a recombinant irrelevant liver specific control, the F alloantigen. The antibodies were also used to probe blots of human, bovine, mouse and rat mitochondria. Finally, fine specificity was studied by selective ELISA and absorption against overlapping expressing fragments of PDC-E2. All five monoclonals, but none of the other mitochondrial autoantigens were specific for PDC-E2. In fact, although affinity purified antibodies to PDC-E2 from patients with PBC cross-reacted with protein X, the human monoclonals did not, suggesting that protein X contains an epitope distinct from that found on PDC-E2. Additionally, all three IgG2 monoclonals recognized distinct epitopes within the inner lipoyl domain of PDC-E2. © 1992.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Leung, PSC
Krams, S
Munoz, S
Surh, CP
Ansari, A
Kenny, T
Robbins, DL
Fung, J
Starzl, TEtes11@pitt.eduTES11
Maddrey, W
Coppel, RL
Gershwin, ME
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1992
Date Type: Publication
Journal or Publication Title: Journal of Autoimmunity
Volume: 5
Number: 6
Page Range: 703 - 718
DOI or Unique Handle: 10.1016/0896-8411(92)90187-u
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0896-8411
Other ID: uls-drl:31735062113240, Starzl CV No. 1531
Date Deposited: 08 Apr 2010 17:26
Last Modified: 16 Oct 2017 05:55
URI: http://d-scholarship.pitt.edu/id/eprint/4917

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