Maeurer M J, Trinder P K, Störkel S, Loos M
Institute of Medical Microbiology, Johannes Gutenberg University, Mainz, Germany.
Immunobiology. 1992 Jun;185(1):103-20. doi: 10.1016/S0171-2985(11)80321-9.
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.
在本报告中，我们能够证明，在易患关节炎的DBA/1小鼠（H2q）皮内注射鸡II型胶原（CII）之前，静脉注射（第0天）人C1q A链的九肽（第26 - 34位氨基酸残基，命名为肽A - C1q），可导致多形核中性粒细胞（PMN）向关节内浸润的现象消失。该九肽表现出表位特征，且与CB11（鸡CII的溴化氰片段，已知含有关节炎诱导和抑制决定簇）的第137 - 147位氨基酸残基具有高度同源性。关节炎指数在静脉注射CII预处理的动物（作为内部对照）中最低，不过静脉注射肽K（来自CB11的第137 - 147位氨基酸残基，额外带有一个甘氨酸残基）或肽A - C1q预处理的动物表现出类似的关节炎指数。只有在关节炎阳性对照组（第0天：静脉注射PBS）中，皮内注射CII才导致PMN侵入滑膜层和关节腔。对静脉免疫（第0天）和CII激发（第7天）后第48天的抗体（Ab）反应分析显示，存在针对天然CII以及天然C1q的IgE抗体。对CII的IgG滴度在肽A - C1q预处理的动物中最高。该组中针对肽A - C1q（免疫抗原）具有活性的抗体主要为IgG1和IgG3亚型。在DBA/1小鼠中，在皮内注射CII之前静脉注射肽A - C1q或CII后对免疫反应的评估显示，对肽A - C1q和肽K有IgM反应，但对CII没有。静脉注射肽A - C1q导致产生仅与肽A - C1q和肽K反应，而不与天然CII反应的IgG3抗体。此外，静脉注射肽A - C1q引发了对一种五肽的IgG反应，该五肽类似于C1q A链的第26 - 30位氨基酸残基（K - G - E - Q - G）。这个五残基抗原决定簇存在于肽K、鸡和人CII以及人C1q中。未检测到对任何测试抗原的特异性IgE反应。由于来自C1q A链的一种肽既能引发免疫反应又能调节小鼠中CII诱导的关节炎，我们推测胶原样补体成分C1q参与了CII诱导的炎性关节炎病变的发展，并且在体内可能代表在透明软骨中的CII作为抗原可用之前诱导抗胶原抗体的早期抗原。
