Functional definition of a B cell epitope, KGEQGEPGA, on C1q the Fc-binding subunit of the first component of complement
| Autor: | P K, Trinder, E, Märker-Hermann, M, Loos, M J, Maeurer |
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| Rok vydání: | 1999 |
| Předmět: |
Mice
Nude Enzyme-Linked Immunosorbent Assay Autoantigens Autoimmune Diseases Arthritis Rheumatoid Mice Agammaglobulinemia Agammaglobulinaemia Tyrosine Kinase Animals Humans Lupus Erythematosus Systemic Complement Pathway Classical Autoantibodies Mice Knockout Mice Inbred BALB C Immunodominant Epitopes Arthritis Complement C1q Antibodies Monoclonal Protein-Tyrosine Kinases Antigens T-Independent Immunoglobulin Class Switching Mice Inbred C57BL Immunoglobulin M Mice Inbred DBA Immunoglobulin G Immunization ISCOMs |
| Zdroj: | Scandinavian journal of immunology. 50(6) |
| ISSN: | 0300-9475 |
| Popis: | A synthetic peptide representing the C1q epitope KGEQGEPGA has been shown to suppress or delay the onset of CII-induced arthritis when applied intravenously (i.v.) prior to an intradermal (i.d.) challenge, in a mouse model; the phenomenon being associated with the development of immunoglobulin (Ig)M antibodies specific for the KGEQGEPGA epitope. Here we show that this amino acid sequence provides an immunodominant B cell epitope that is recognised by autoantibodies present in the sera of patients with chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, two diseases associated with an immune response to C1q. The peptide's ability to produce peptide specific IgM when applied i.v. in both normal and athymic mice but not in mice exhibiting the x-linked B-cell associated Bruton's tyrosine kinase defect permits classification of the KGEQGEPGA peptide as a T-cell independent antigen type-2 (TI-2). IgM monoclonal antibodies raised against the peptide are able to functionally block activation of the complement cascade by C1q, via a mechanism that inhibits the C4 consumption. Antibodies to this immunodominant epitope may therefore modulate inflammatory processes by interfering with the activation of the classical pathway of the complement. |
| Databáze: | OpenAIRE |
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