Induction of arthritis with monoclonal antibodies to collagen.
Induction of arthritis with monoclonal antibodies to collagen.
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DOI：
10.4049/jimmunol.148.7.2103
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发表时间：
1992-04
影响因子：
4.4
通讯作者：
K. Terato;K. Hasty;R. Reife;M. Cremer;A. Kang;J. Stuart
中科院分区：
文献类型：
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作者：
K. Terato;K. Hasty;R. Reife;M. Cremer;A. Kang;J. Stuart
用鸡Ⅱ型胶原免疫DBA/1小鼠，制备了单克隆抗体。共分离并表征了69种IgG抗体。大多数（36%）与CNBr衍生的肽CB 11反应，该肽先前被鉴定为含有主要的免疫原性和致关节炎性表位。与CB 11反应的7种抗体与小鼠II型胶原蛋白强烈交叉反应。这些被给予DBA/1小鼠，试图诱导关节炎。单个抗体能够诱导由最小滑膜增生组成的轻度病变，但不诱导明显的关节炎。然而，抗体的组合诱导严重的关节炎，关节软骨的显着破坏。最低有效组合由三种抗体组成。关节炎在注射抗体后48至72小时内发生，并持续3周的观察期。每隔一段时间测量抗体水平，并持续3周观察期，尽管水平不断下降。竞争性结合试验表明，每种有效的抗体独立结合，这表明某些空间或定量关系是重要的，可能与它们激活补体的能力有关。
mAb were developed from DBA/1 mice immunized with chick type II collagen. A total of 69 IgG antibodies was isolated and characterized. The majority (36%) reacted with a CNBr-derived peptide CB11 previously identified as containing a major immunogenic and arthritogenic epitope(s). Seven of the antibodies reactive with CB11 crossreacted strongly with mouse type II collagen. These were administered to DBA/1 mice in an attempt to induce arthritis. Individual antibodies were able to induce mild lesions consisting of minimal synovial proliferation but not overt arthritis. However, a combination of antibodies induced severe arthritis with marked destruction of articular cartilage. The minimal effective combination consisted of three antibodies. Arthritis developed within 48 to 72 h after injection of the antibodies and persisted for the duration of the observation period of 3 wk. Antibody levels were measured at intervals and persisted for the 3 wk observation period although at diminishing levels. Competitive binding assays demonstrated that each of the effective antibodies bound independently suggesting that some spatial or quantitative relationship was important possibly related to their ability to activate complement.