Details

Autor(en) / Beteiligte

• Shimoda, Shinji
• Nakamura, Minoru
• Ishibashi, Hiromi
• Kawano, Akira
• Kamihira, Takashi
• Sakamoto, Norihiro
• Matsushita, Sho
• Tanaka, Atsushi
• Worman, Howard J
• Gershwin, M.Eric
• Harada, Mine

Titel

Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis

Ist Teil von

• Gastroenterology (New York, N.Y. 1943), 2003-06, Vol.124 (7), p.1915-1925

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• The mechanism for development of primary biliary cirrhosis (PBC) remains enigmatic, but molecular mimicry has been implicated because of well-known cross-reactivity of human mitochondrial autoantigens and equivalent bacterial antigens. Virtually all patients with PBC have antimitochondrial autoantibodies (AMA), but, interestingly, approximately 50% also manifest antinuclear antibodies (ANA). To determine whether generation of ANA are due to molecular mimicry of mitochondrial peptides, we established 6 T-cell clones selected by a peptide corresponding to the E2 subunit of mitochondrial pyruvate dehydrogenase complex and analyzed for reactivity to mimicry peptides derived from mitochondrial and nuclear autoantigens, including control sequences. For mitochondrial autoantigens, 1 peptide from the E2 subunit of the pyruvate dehydrogenase complex, 1 peptide from the E2 subunit of the oxo-glutarate dehydrogenase complex, 1 peptide from the E2 subunit of the branched-chain 2-oxoacid dehydrogenase complex, and 1 peptide from the E3-binding protein cross-reacted with these T-cell clones. For the nuclear autoantigens, 5 peptides from gp210 and 1 from Sp100 cross-reacted with these clones. Furthermore, 1 of 3 T-cell clones selected by recombinant gp210 protein reacted with a mimicry peptide corresponding to amino acids 188-201 of gp210, indicating that this part of the protein is a naturally processed immunodominant T-cell epitope. These results demonstrate molecular mimicry between mitochondrial and nuclear autoantigens in PBC and that a mimicry peptide may become an immunodominant T-cell epitope. These data have significance not only for PBC but also for the production of ANA in other disease processes.