title: Modulation of type II collagen-induced arthritis in DBA/1 mice by intravenous application of a peptide from the C1q-A chain.
abstract: In this report we are able to show that intravenous (i.v.) application (day 0) of a nonapeptide (residues 26-34) from the human C1q A-chain (designated peptide A-C1q) prior to intradermal (i.d.) administration of chicken type II collagen (CII) in arthritis-susceptible DBA/1 mice (H2q), leads to abrogation of polymorphonuclear neutrophil (PMN) invasion into the joints. This nonapeptide exhibits epitope characteristics and high homology to residues 137-147 of CB11 (a cyanogen bromide fragment of chicken CII, known to contain both arthritis inducing and suppressing determinants). Arthritis index was lowest in animals pretreated i.v. with CII (as internal control), though animals pretreated i.v. with peptide K (residues 137-147 with an additional glycine residue from CB11) or peptide A-C1q exhibited comparative arthritic indices. Only in the arthritis-positive control group (day 0: PBS i.v.) did i.d. application of CII lead to invasion of PMN into the synovial layer and the joint space. Analysis of antibody (Ab) responses at day 48 after i.v. immunization (day 0) and CII challenge (day 7) revealed IgE-Abs to native CII and also to native C1q. IgG titers to CII were highest in animals pretreated with peptide A-C1q. Abs from this group, exhibiting activity to peptide A-C1q (immunizing antigen), were of mainly IgG1 and IgG3 isotypes. Evaluation of the immune response following i.v. application of peptide A-C1q or CII, prior to i.d. CII administration, in DBA/1 mice, revealed IgM responses to peptide A-C1q and peptide K, but not to CII. Intravenous application of peptide A-C1q led to generation of IgG3-Abs reacting only with peptide A-C1q and peptide K, but not with native CII. Additionally, i.v. application of peptide A-C1q elicited IgG responses to a pentapeptide, resembling amino acid residues 26-30 (K-G-E-Q-G) of the C1q A-chain. This five residue antigenic determinant is present in peptide K, in chicken and human CII as well as in human C1q. No specific IgE response to any of the antigens tested could be detected. Since a peptide from the C1q A-chain is both capable of eliciting immune responses and modulating CII-induced arthritis in mice, we postulate that the collagen-like complement component C1q is involved in the development of CII-induced inflammatory arthritic lesions, and may represent, in vivo, the early antigen responsible for inducing anticollagen antibodies prior to CII in hyaline cartilage becoming available as antigen.
authors.affiliation: Institute of Medical Microbiology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
authors.forename: P K
authors.initials: PK
authors.lastname: Trinder
authors.forename: S
authors.initials: S
authors.lastname: Störkel
authors.forename: M
authors.initials: M
authors.lastname: Loos
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001168:Arthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003094:Collagen / Q000008:administration & dosage / Q000276:immunology; D015922:Complement C1q / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D007271:Injections, Intradermal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D009842:Oligopeptides; D010446:Peptide Fragments; D015922:Complement C1q; D003094:Collagen