Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
J Gen Virol. 2010 Jun;91(Pt 6):1577-89. doi: 10.1099/vir.0.019471-0. Epub 2010 Feb 3.
Many of the 51 serotypes of adenovirus have been associated with clinically relevant infection. Adenovirus can disseminate rapidly in patients with a compromised immune system, such as that which occurs secondary to haematopoietic progenitor-cell transplantation. The higher rate of infection in recipients of T cell-depleted grafts and in those undergoing T cell-targeted treatment during graft versus host disease demonstrates the importance of a T-cell response in preventing disseminated infection. Studies have shown that the memory response to adenovirus is directed primarily to the hexon protein and is dominated by CD4+ T cells, probably due to the ability of the virus to block its presentation on HLA class I antigens. We have developed an approach to expand adenovirus-specific T cells using a pool of overlapping pentadecapeptides derived from selected conserved regions of hexon. We characterized responses to identify the peptides that are recognized, the responding T-cell subsets and their HLA restriction. Of eight lines that were characterized extensively, seven included both CD4+ and CD8+ T cells and each recognized between two and eight unique peptide sequences. By focusing the response on the conserved sequences of hexon, the cell lines are likely to recognize most of the serotypes responsible for clinically relevant disease. The 15 aa peptides used to prime the responses are more likely than whole virus or longer peptides to expand the less frequent CD8+ memory subset. Lines prepared by using our method may be more effective in adoptive immunotherapy protocols designed to prevent or treat disseminated adenovirus infections in high-risk patients.
许多 51 种血清型的腺病毒都与临床相关的感染有关。腺病毒在免疫系统受损的患者中迅速传播，例如发生在造血祖细胞移植后的患者中。T 细胞耗竭移植物受者和移植物抗宿主病期间接受 T 细胞靶向治疗的患者中感染率较高，这表明 T 细胞反应在预防播散性感染中很重要。研究表明，对腺病毒的记忆反应主要针对六邻体蛋白，主要由 CD4+T 细胞主导，这可能是由于病毒能够阻止其在 HLA I 类抗原上的呈递。我们开发了一种使用源自六邻体选定保守区的重叠十五肽池来扩增腺病毒特异性 T 细胞的方法。我们对反应进行了特征分析，以确定被识别的肽、反应的 T 细胞亚群及其 HLA 限制。在经过广泛表征的 8 条系中，有 7 条系包含 CD4+和 CD8+T 细胞，每条系都识别 2 到 8 个独特的肽序列。通过将反应集中在六邻体的保守序列上，细胞系很可能识别导致临床相关疾病的大多数血清型。用于引发反应的 15 个氨基酸肽比全病毒或更长的肽更有可能扩增不太常见的 CD8+记忆亚群。使用我们的方法制备的系可能更有效，适用于设计用于预防或治疗高危患者播散性腺病毒感染的过继免疫治疗方案。
