Molecular mimicry mediated by MHC class Ib molecules after infection with Gram-negative pathogens
Molecular mimicry mediated by MHC class Ib molecules after infection with Gram-negative pathogens
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DOI：
10.1038/72329
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发表时间：
2000-02-01
期刊：
影响因子：
82.9
通讯作者：
Soloski, MJ
中科院分区：
文献类型：
--
作者：
Lo, WF;Woods, AS;Soloski, MJ
许多自身免疫性疾病的发生在病因学上与接触感染因子有关（1）。例如，有沙门氏菌感染史的一部分患者发生反应性关节炎（2-6）。关节炎组织中细菌抗原的持续存在以及从反应性关节炎患者的关节中分离出沙门氏菌或耶尔森氏菌反应性CD 8（+）T细胞支持革兰氏阴性细菌感染和自身免疫性疾病之间的病因学联系（7，8）。提出的解释感染和自身免疫之间联系的模型包括炎症诱导的隐蔽自身表位呈递、抗原持久性和分子模拟（1）。一些研究支持分子模拟作为II类表位参与感染性疾病诱导的自身反应性的机制（9-12）。在这里，我们已经确定了一个免疫显性表位来源于S。鼠伤寒GroEL分子。该表位由小鼠H2-T23编码的Ib类分子Qa-1呈递，并被自然感染后诱导的CD 8（+）细胞毒性T淋巴细胞识别。S.识别GroEL表位的鼠伤寒沙门氏菌刺激的细胞毒性T淋巴细胞与来自小鼠热休克蛋白60的肽交叉反应，并识别应激的巨噬细胞。我们的研究结果表明，感染诱导的自身免疫识别的MHC Ib类分子的参与，并指出革兰氏阴性细菌感染和自身免疫之间的病因学联系的机制。
The development of many autoimmune diseases has been etiologically linked to exposure to infectious agents(1). For example, a subset of patients with a history of Salmonella infection develop reactive arthritis(2-6). The persistence of bacterial antigen in arthritic tissue and the isolation of Salmonella or Yersinia reactive CD8(+) T cells from the joints of patients with reactive arthritis support the etiological link between Gram-negative bacterial infection and autoimmune disease(7,8). Models proposed to account for the link between infection and autoimmunity include inflammation-induced presentation of cryptic self-epitopes, antigen persistence and molecular mimicry(1). Several studies support molecular mimicry as a mechanism for the involvement of class II epitopes in infectious disease-induced self-reactivity(9-12). Here, we have identified an immunodominant epitope derived from the S. typhimurium GroEL molecule. This epitope is presented by the mouse H2-T23-encoded class Ib molecule Qa-l and was recognized by CD8(+) cytotoxic T lymphocytes induced after natural infection. S. typhimurium-stimulated cytotoxic T lymphocytes recognizing the GroEL epitope cross-reacted with a peptide derived from mouse heat shock protein 60 and recognized stressed macrophages. Our results indicate involvement of MHC class ib molecules in infection-induced autoimmune recognition and indicate a mechanism for the etiological link between Gram-negative bacterial infection and autoimmunity.