HTLV-I env protein acts as a major antigen in patients with HTLV-I-associated arthropathy
HTLV-I env protein acts as a major antigen in patients with HTLV-I-associated arthropathy
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DOI：
10.1007/s10067-004-0901-z
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发表时间：
2004-10-01
影响因子：
3.4
通讯作者：
Nishioka, K
中科院分区：
文献类型：
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作者：
Kato, T;Asahara, H;Nishioka, K
我们的目的是研究 HTLV-I（人类 T 细胞白血病病毒 I 型）相关慢性关节炎 (HAAP) 的病理机制，涉及 T 细胞对 HTLV-I 病毒蛋白的反应。我们通过组织学、单链构象多态性 (SSCP) 分析和 T 细胞受体 (TCR) 测序，检查了 HAAP 患者发炎滑膜的 T 细胞克隆性和 T 细胞识别的抗原。 SSCP 分析显示滑膜中 T 细胞的寡克隆扩增，表明存在抗原介导的刺激。相比之下，外周血淋巴细胞（PBL）的克隆扩增较少。在受影响的滑膜以及 PBL 中检测到 HTLV-1 env 和tax mRNA 的表达。滑膜中的许多 T 细胞克隆识别 HTLV-1 env 和tax 蛋白。 109 个检查的关节 T 细胞克隆中有 27 个 (24.9%) 具有 HTLV-I env 反应性，7 个克隆 (6.4%) 具有 HTLV-I Tax 反应性。滑膜T细胞的连接序列分析显示HTLV-I env和tax反应性T细胞的互补决定区3（CDR3）中缺乏高度保守的氨基酸基序，表明这些细胞识别HTLV-I抗原上的多个T细胞表位。这些发现表明，HTLV-I env 蛋白作为主要抗原，可能在 HAAP 患者关节病的发展中发挥作用。
Our objective was to investigate the pathological mechanisms of HTLV-I (human T-cell leukemia virus type I)-associated chronic arthritis (HAAP) with respect to T-cell response to HTLV-I viral proteins. We examined T-cell clonality and the antigen recognized by T cells from the inflamed synovium of patients with HAAP by using histology, a single-strand conformation polymorphism (SSCP) analysis and T cell receptor (TCR) sequencing. The SSCP analysis showed oligoclonal expansion of T cells in the synovium, suggesting an antigen-mediated stimulation. In contrast, there was less clonal expansion in peripheral blood lymphocytes (PBL). The expression of HTLV-1 env and tax mRNA was detected in the affected synovium as well as in PBL. A number of T-cell clones in the synovium recognized HTLV-I env and tax proteins. Twenty-seven (24.9%) of 109 examined T-cell clones in the joints were HTLV-I env reactive, and 7 clones (6.4%) were HTLV-I tax reactive. Junctional sequence analysis of synovial T cells showed a lack of highly conserved amino acid motifs in the complementarity-determining region 3 (CDR3) of HTLV-I env and tax reactive T cells, suggesting that these cells recognized multiple T-cell epitopes on HTLV-I antigen. These findings suggest that HTLV-I env protein acts as a major antigen and may play a role in the development of arthropathy in patients with HAAP.