Defining a T‐cell epitope within HSP 65 in recurrent aphthous stomatitis
Defining a T‐cell epitope within HSP 65 in recurrent aphthous stomatitis
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DOI：
10.1046/j.1365-2249.2002.01757.x
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发表时间：
2002-05
影响因子：
4.6
通讯作者：
A. Hasan;T. Shinnick;Y. Mizushima;R. Zee;T. Lehner
中科院分区：
文献类型：
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作者：
A. Hasan;T. Shinnick;Y. Mizushima;R. Zee;T. Lehner
65 kD热休克蛋白（HSP）与复发性口疮性口炎（RAS）的病因有关。我们之前已经证明，从分枝杆菌65kd HSP序列中提取的肽91-105特异性刺激RAS患者的淋巴细胞。在这项研究中，我们发现分枝杆菌肽91-105显著刺激CD4+和CD8+ T细胞。相比之下，人同源肽116-130仅刺激CD4+ T细胞。抑制研究显示CD4+ T细胞为II类限制，而CD8+ T细胞为I类限制。然后，我们使用截断或取代的肽，并证明残基95-105在刺激T细胞中似乎很重要，而残基104（Arg）至关重要。因此，肽95 - 105可能在RAS中构成T细胞增殖表位。我们推测，大量的微生物在口腔黏膜上定居，可能通过微生物HSP 65衍生的肽95-105引发免疫应答，刺激口腔黏膜中大量的朗格汉斯细胞激活对上皮HSP 60内同源肽116-130的交叉反应免疫应答，引发导致RAS的免疫病理变化。
The 65 kD heat shock protein (HSP) has been implicated in the aetiology of recurrent aphthous stomatitis (RAS). We have previously demonstrated that peptide 91–105 derived from the sequence of mycobacterial 65 kD HSP stimulates specifically lymphocytes from patients with RAS. In this investigation, we show that both CD4+ and CD8+ T cells were significantly stimulated with mycobacterial peptide 91–105. In contrast, the human homologous peptide 116–130 stimulated only CD4+ T cells. Inhibition studies showed that CD4+ T cells were class II restricted, whereas CD8+ T cells were class I restricted. We then used truncated or substituted peptides, and demonstrated that residues 95–105 appear to be important, and residue 104(Arg) critical, in stimulating the T cells. Thus, peptide 95– 105 may constitute a T‐cell proliferative epitope in RAS. We postulate that the high load of micro‐organisms that colonize the oral mucosa may initiate an immune response by the microbial HSP 65‐derived peptide 95–105, stimulating the numerous Langerhans cells in the oral mucosa to activate a cross‐reacting immune response to the homologous peptide 116–130 within the epithelial HSP 60, initiating the immunopathological changes that lead to RAS.