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
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID  |
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Leung, PSC | | | | Krams, S | | | | Munoz, S | | | | Surh, CP | | | | Ansari, A | | | | Kenny, T | | | | Robbins, DL | | | | Fung, J | | | | Starzl, TE | tes11@pitt.edu | TES11 | | Maddrey, W | | | | Coppel, RL | | | | Gershwin, ME | | | |
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Centers: |
Other Centers, Institutes, Offices, 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: |
02 Feb 2019 13:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/4917 |
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