Lamonaca V, Missale G, Urbani S, Pilli M, Boni C, Mori C, Sette A, Massari M, Southwood S, Bertoni R, Valli A, Fiaccadori F, Ferrari C
Laboratorio di Immunopatologia Virale, Divisione Malattie Infettive, Azienda Ospedaliera di Parma, and Cattedra di Malattie Infettive, Università di Parma, Italy.
Hepatology. 1999 Oct;30(4):1088-98. doi: 10.1002/hep.510300435.
The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.
人们认为，HLA II类分子限制的针对丙型肝炎病毒（HCV）抗原的T细胞反应会影响丙型肝炎的最终结局，因为在从急性丙型肝炎中康复的患者中这种反应很强烈，但在发生慢性感染的患者中则很微弱。因此，在慢性HCV感染中对外源性T细胞反应进行刺激可能是一种治疗慢性丙型肝炎患者的策略，即通过使他们的T细胞反应活性接近成功从肝炎中康复的患者的反应活性来实现。这也可能是一种预防方法，通过在感染的早期阶段促进强烈的保护性反应的发展来避免病毒传播。由免疫显性、多反应性和保守的T细胞表位组成的基于T细胞的疫苗可能是实现T细胞反应活性最佳刺激的有力工具。为了鉴定用于此目的的HLA II类分子限制的T细胞表位，对22名急性HCV感染患者进行了研究，并平均随访了29个月。其中8人从肝炎中康复，14人发展为慢性感染。使用覆盖整个核心和NS4抗原的重叠20肽以及一组代表核心、NS3、NS4和NS5高度保守区域的肽。通过直接外周血T细胞刺激以及对HCV特异性T细胞系和克隆的精细特异性分析，在核心、NS3和NS4内鉴定出了高免疫原性的T细胞表位。所有这些表位在已知的HCV分离株中都是免疫显性且高度保守的。此外，它们具有多反应性，因为它们可以由不同的HLA II类分子呈递给T细胞。免疫显性、序列保守性和多反应性使这些表位成为针对HCV的预防性或治疗性基于T细胞的疫苗的理想成分。
