Ho On, Green William R
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
J Immunol. 2006 Feb 15;176(4):2470-5. doi: 10.4049/jimmunol.176.4.2470.
Cytolytic CD8(+) T cells (CTL) are key to the immune response that controls virus infections and mediates disease protection. The ability of CTL to induce apoptosis of infected cells and/or limit viral replication is determined by recognition of processed viral peptide epitopes on the surface of the target cell. An understudied source of MHC class I-presented peptides is the aptly named "cryptic epitopes," defined by their nontraditional methods of generation, including derivation from alternative reading frames (ARFs). Although ARF-encoded epitopes have now been documented in a few systems, their potential functional relevance in vivo has been debated. In this study, we demonstrate the physiological significance of an ARF-derived CTL epitope in a retrovirus-induced disease model. We show that disease-susceptible CD8-deficient mice reconstituted with CTL specific for the retroviral ARF-derived SYNTGRFPPL epitope controlled an infection by the LP-BM5 retrovirus isolate, evidently at the level of viral clearance, resulting in protection of these mice from disease. These data indicate that ARF-derived epitopes are indeed relevant inducers of the immune system and demonstrate the importance of atypically generated peptides as functional Ag with a physiologic role in disease protection.
细胞溶解性CD8(+) T细胞（CTL）是控制病毒感染并介导疾病保护的免疫反应的关键。CTL诱导受感染细胞凋亡和/或限制病毒复制的能力取决于对靶细胞表面加工后的病毒肽表位的识别。I类主要组织相容性复合体（MHC）提呈的肽的一个研究较少的来源是恰当地命名为“隐蔽表位”，其定义为通过非传统方式产生，包括源自可变阅读框（ARF）。尽管现在已经在一些系统中记录了ARF编码的表位，但它们在体内的潜在功能相关性一直存在争议。在本研究中，我们在逆转录病毒诱导的疾病模型中证明了ARF衍生的CTL表位的生理意义。我们表明，用对逆转录病毒ARF衍生的SYNTGRFPPL表位具有特异性的CTL重建的疾病易感CD8缺陷小鼠控制了LP - BM5逆转录病毒分离株的感染，显然是在病毒清除水平，从而保护这些小鼠免于疾病。这些数据表明，ARF衍生的表位确实是免疫系统的相关诱导物，并证明了非典型产生的肽作为在疾病保护中具有生理作用的功能性抗原的重要性。
