Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis.
Shinji Shimoda,Shinji Shimoda,Judith A Van de Water,Aftab A. Ansari,Minoru Nakamura,Hiromi Ishibashi,Ross L. Coppel,John R. Lake,Emmet B. Keeffe,Thomas E. Roche,M. Eric Gershwin +10 more
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TLDR
Results showed a disease-specific 100-150-fold increase in the precursor frequency of PDC-E2 163-176-specific T cells in the hilar lymph nodes and liver when compared with PBMC from PBC patients, providing evidence for a major role for PDC -E2 peptide 163- 176 and/or peptides bearing a similar motif in the pathogenesis of PBC.Abstract:
The immunodominant antimitochondrial antibody response in patients with primary biliary cirrhosis (PBC) is directed against the E2 component of the pyruvate dehydrogenase complex (PDC-E2). Based on our earlier observations regarding peripheral blood mononuclear cell (PBMC) T cell epitopes, we reasoned that a comparative analysis of the precursor frequencies of PDC-E2 163-176-specific T cells isolated from PBMC, regional hepatic lymph nodes, and from the liver of PBC patients would provide insight regarding the role of T cells in PBC. Results showed a disease-specific 100-150-fold increase in the precursor frequency of PDC-E2 163-176-specific T cells in the hilar lymph nodes and liver when compared with PBMC from PBC patients. Interestingly, autoreactive T cells and autoantibodies from PBC patients both recognize the same dominant epitope. In addition, we demonstrated cross-reactivity of PDC-E2 peptide 163-176-specific T cell clones with PDC-E2 peptide 36-49 and OGDC-E2 peptide 100-113 thereby identifying a common T cell epitope "motif" ExETDK. The peptide 163-176-specific T cell clones also reacted with purified native PDC-E2, suggesting that this epitope is not a cryptic determinant. These data provide evidence for a major role for PDC-E2 peptide 163-176 and/or peptides bearing a similar motif in the pathogenesis of PBC.read more
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Journal ArticleDOI
Primary biliary cirrhosis.
TL;DR: Mise a jour: anatomopathologie, anomalies immunologiques et pathogenese, tests de laboratoire, manifestations cliniques et troubles associes, evolution, traitement.
Journal ArticleDOI
Primary Biliary Cirrhosis
Keith D. Lindor,M. Eric Gershwin,Raoul Poupon,Marshall M. Kaplan,Nora V. Bergasa,E. Jenny Heathcote +5 more
TL;DR: PBC is a chronic cholestatic liver disease characterized by high-titer serum antimitochondrial autoantibodies (AMAs) and autoimmune-mediated destruction of small and medium-sized intrahepatic bile ducts as discussed by the authors.
Journal ArticleDOI
Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases.
TL;DR: This American Association for the Study of Liver Diseases (AASLD) 2018 Practice Guidance on Primary Biliary Cholangitis is an update of the PBC guidelines published in 2009, and provides a data-supported approach to screening, diagnosis, and clinical management of patients with PBC.
Journal ArticleDOI
Primary biliary cirrhosis: an orchestrated immune response against epithelial cells.
M. Eric Gershwin,Aftab A. Ansari,Ian R. Mackay,Yasuni Nakanuma,Akiyoshi Nishio,Merrill J. Rowley,Ross L. Coppel +6 more
TL;DR: The data so far provide suggestive evidence that PBC is a mucosal disease; this thesis provides a basis for discussion of etiology via the enterohepatic circulation of toxins and/or infection.
Journal ArticleDOI
Identification of HLA-A2-restricted CD8(+) cytotoxic T cell responses in primary biliary cirrhosis: T cell activation is augmented by immune complexes cross-presented by dendritic cells.
Hiroto Kita,Zhe-Xiong Lian,Judy Van de Water,Xiao-Song He,Shuji Matsumura,Marshall M. Kaplan,Velimir A. Luketic,Ross L. Coppel,Aftab A. Ansari,M. Eric Gershwin +9 more
TL;DR: Using peripheral blood mononuclear cells from PBC, an HLA-A2–restricted CTL epitope of the E2 component of pyruvate dehydrogenase (PDC-E2) is identified, the immunodominant mitochondrial autoantigen, which for the first time defines a unique role for autoantibodies in the pathogenesis of an autoimmune disease.
References
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Journal ArticleDOI
Primary biliary cirrhosis.
TL;DR: Mise a jour: anatomopathologie, anomalies immunologiques et pathogenese, tests de laboratoire, manifestations cliniques et troubles associes, evolution, traitement.
Journal ArticleDOI
Molecular mimicry in T cell-mediated autoimmunity: Viral peptides activate human T cell clones specific for myelin basic protein
TL;DR: In this paper, structural similarity between viral T cell epitopes and self-peptides could lead to the induction of an autoaggressive T cell response based on the structural requirements for both MHC class 11 binding and TCR recognition of an immunodominant myelin basic protein (MBP) peptide.
Journal ArticleDOI
Antigen-specific interaction between T and B cells
TL;DR: In this article, the authors have cloned and immortalized human antigen-specific B cells with Epstein-Barr virus (EBV) and analyzed their interaction with T-cell clones specific for the same antigen.
Journal ArticleDOI
Primary Biliary Cirrhosis
Keith D. Lindor,M. Eric Gershwin,Raoul Poupon,Marshall M. Kaplan,Nora V. Bergasa,E. Jenny Heathcote +5 more
TL;DR: PBC is a chronic cholestatic liver disease characterized by high-titer serum antimitochondrial autoantibodies (AMAs) and autoimmune-mediated destruction of small and medium-sized intrahepatic bile ducts as discussed by the authors.
Journal ArticleDOI
Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen.
TL;DR: In mice with chronic EAE, several additional determinants of MBP in peptides 35–47, 81–100 and 121–140 recall proliferative responses and reactivity to the latter determinants was also detected after induction of EAE with MBP peptide Ac1–11 alone, demonstrating priming by endogenous MBP determinants.