Artikel ; Online: Epitope-specific antibody response is controlled by immunoglobulin V(H) polymorphisms.
The Journal of experimental medicine
2014 Band 211, Heft 3, Seite(n) 405–411
Abstract: Autoantibody formation is essential for the development of certain autoimmune diseases like rheumatoid arthritis (RA). Anti-type II collagen (CII) antibodies are found in RA patients; they interact with cartilage in vivo and are often highly pathogenic ... ...
| Abstract | Autoantibody formation is essential for the development of certain autoimmune diseases like rheumatoid arthritis (RA). Anti-type II collagen (CII) antibodies are found in RA patients; they interact with cartilage in vivo and are often highly pathogenic in the mouse. Autoreactivity to CII is directed to multiple epitopes and conserved between mice and humans. We have previously mapped the antibody response to CII in a heterogeneous stock cohort of mice, with a strong association with the IgH locus. We positioned the genetic polymorphisms and determined the structural requirements controlling antibody recognition of one of the major CII epitopes. Polymorphisms at positions S31R and W33T of the associated variable heavy chain (VH) allele were identified and confirmed by gene sequencing. The Fab fragment binding the J1 epitope was crystallized, and site-directed mutagenesis confirmed the importance of those two variants for antigen recognition. Back mutation to germline sequence provided evidence for a preexisting recognition of the J1 epitope. These data demonstrate a genetic association of epitope-specific antibody responses with specific VH alleles, and it highlights the importance of germline-encoded antibodies in the pathogenesis of antibody-mediated autoimmune diseases. |
|---|---|
| Mesh-Begriff(e) | Animals ; Antibody Formation/genetics ; Antibody Formation/immunology ; Arthritis, Rheumatoid/immunology ; Autoantibodies/immunology ; Base Sequence ; Collagen Type II/genetics ; Collagen Type II/immunology ; Crystallography ; Epitopes/genetics ; Humans ; Immunoglobulin Heavy Chains/chemistry ; Immunoglobulin Heavy Chains/genetics ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Polymorphism, Genetic/genetics ; Protein Conformation ; Sequence Analysis, DNA ; Surface Plasmon Resonance |
| Chemische Substanzen | Autoantibodies ; Collagen Type II ; Epitopes ; Immunoglobulin Heavy Chains |
| Sprache | Englisch |
| Erscheinungsdatum | 2014-02-17 |
| Erscheinungsland | United States |
| Dokumenttyp | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 218343-2 |
| ISSN | 1540-9538 ; 0022-1007 |
| ISSN (online) | 1540-9538 |
| ISSN | 0022-1007 |
| DOI | 10.1084/jem.20130968 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
Zusatzmaterialien
Kategorien
Verfügbar in ZB MED Köln/Königswinter
| Ua VI Zs.107: Hefte anzeigen | Standort: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
|||
| Zs.MG 45: Hefte anzeigen |
Über subito bestellen
Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.