MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines.
MHC class I antigen presentation and implications for developing a new generation of therapeutic vaccines.
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DOI：
10.1177/2051013614525375
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发表时间：
2014-05-01
期刊：
影响因子：
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通讯作者：
Philip, Ramila
中科院分区：
文献类型：
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作者：
Comber, Joseph D;Philip, Ramila
主要组织相容性复合物I类（MHC-I）呈递的肽表位为细胞中发生的变化提供了“窗口”。通常，这些肽通过胞质溶胶中内源性合成的蛋白质的蛋白水解产生，负载到MHC-I分子上，并呈递在细胞表面上以供CD 8（+）T细胞监视。MHC-I限制性加工和呈递提醒免疫系统任何细胞内展开的感染或致瘤过程，并为细胞毒性T细胞应答提供潜在靶点。因此，理论上，基于MHC-I呈递的肽表位的治疗性疫苗可以诱导CD 8（+）T细胞应答，这对肿瘤根除和患者存活具有切实的临床影响。三种主要的方法已被用来确定MHC-I限制性表位，包括在基于肽的癌症疫苗：遗传，基序预测，最近，免疫蛋白质组学分析。尽管前两种方法能够鉴定T细胞刺激性表位，但这些方法具有显著的缺点，并且可能不能准确地代表肿瘤细胞呈递的表位。相比之下，免疫蛋白质组学方法可以克服这些缺点，并鉴定天然加工和呈递的肿瘤相关表位，其诱导更临床相关的肿瘤特异性细胞毒性T细胞应答。在这篇综述中，我们讨论了使用天然呈递的MHC-I肽库在配制肽疫苗中的重要性，基于肽的疫苗在各种癌症中的最新应用，并强调了肽疫苗的当前状态的优点和缺点。
Major histocompatibility complex class I (MHC-I) presented peptide epitopes provide a 'window' into the changes occurring in a cell. Conventionally, these peptides are generated by proteolysis of endogenously synthesized proteins in the cytosol, loaded onto MHC-I molecules, and presented on the cell surface for surveillance by CD8(+) T cells. MHC-I restricted processing and presentation alerts the immune system to any infectious or tumorigenic processes unfolding intracellularly and provides potential targets for a cytotoxic T cell response. Therefore, therapeutic vaccines based on MHC-I presented peptide epitopes could, theoretically, induce CD8(+) T cell responses that have tangible clinical impacts on tumor eradication and patient survival. Three major methods have been used to identify MHC-I restricted epitopes for inclusion in peptide-based vaccines for cancer: genetic, motif prediction and, more recently, immunoproteomic analysis. Although the first two methods are capable of identifying T cell stimulatory epitopes, these have significant disadvantages and may not accurately represent epitopes presented by a tumor cell. In contrast, immunoproteomic methods can overcome these disadvantages and identify naturally processed and presented tumor associated epitopes that induce more clinically relevant tumor specific cytotoxic T cell responses. In this review, we discuss the importance of using the naturally presented MHC-I peptide repertoire in formulating peptide vaccines, the recent application of peptide-based vaccines in a variety of cancers, and highlight the pros and cons of the current state of peptide vaccines.