Department of Paediatric Immunology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands.
Ann Rheum Dis. 2010 Jan;69(1):255-62. doi: 10.1136/ard.2008.103978.
To explore potential T-cell epitopes of the core protein of human cartilage proteoglycan aggrecan (PG) in patients with rheumatoid arthritis (RA) or osteoarthritis.
Peptide-specific T-cell proliferation and cytokine/chemokine production in response to PG-specific peptides were measured in RA and osteoarthritis patients and in healthy controls.
Peptides representing amino acid regions 16-39 and 263-282 of PG were most frequently recognised by T cells in a subset of patients with RA or osteoarthritis. Peripheral blood mononuclear cells from these PG-reactive RA and osteoarthritis patients showed increased production of proinflammatory cytokines/chemokines in response to PG peptide stimulation. As PG p263-282 was found to show high sequence homology with Yersinia Yop protein, the corresponding bacterial (Yersinia) peptide was also tested. Remarkably, RA and osteoarthritis patients responding to the Yersinia peptide also responded to p263-282 of PG suggesting a possibility of molecular mimicry in these patients.
These results indicate that PG-specific peptides, located in the G1 domain of PG, can induce (auto)antigenic T-cell responses in RA and osteoarthritis patients. These peptides might thus be involved in the immune pathogenesis and/or cartilage degradation in RA and osteoarthritis.
探索人类软骨蛋白聚糖核心蛋白（PG）在类风湿关节炎（RA）或骨关节炎患者中的潜在 T 细胞表位。
在 RA 和骨关节炎患者及健康对照者中，测量针对 PG 特异性肽的肽特异性 T 细胞增殖和细胞因子/趋化因子产生情况。
在 RA 或骨关节炎患者的亚组中，代表 PG 氨基酸区域 16-39 和 263-282 的肽最常被 T 细胞识别。来自这些 PG 反应性 RA 和骨关节炎患者的外周血单核细胞在受到 PG 肽刺激时显示出促炎细胞因子/趋化因子的产生增加。由于 PG p263-282 与耶尔森氏菌 Yop 蛋白具有高度序列同源性，因此还测试了相应的细菌（耶尔森氏菌）肽。值得注意的是，对耶尔森氏菌肽有反应的 RA 和骨关节炎患者也对 PG 的 p263-282 有反应，这表明这些患者可能存在分子模拟。
这些结果表明，位于 PG G1 结构域的 PG 特异性肽可在 RA 和骨关节炎患者中诱导（自身）抗原性 T 细胞反应。这些肽可能参与 RA 和骨关节炎的免疫发病机制和/或软骨降解。
