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.