Human CD4+ T cells stimulated by conserved adenovirus 5 hexon peptides recognize cells infected with different species of human adenovirus
Human CD4+ T cells stimulated by conserved adenovirus 5 hexon peptides recognize cells infected with different species of human adenovirus
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DOI：
10.1002/eji.200535786
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发表时间：
2006-09-01
影响因子：
5.4
通讯作者：
Schilham, Marco W.
中科院分区：
文献类型：
--
作者：
Veltrop-Duits, Louise A.;Heemskerk, Bianca;Schilham, Marco W.
针对人腺病毒（HAdV）的免疫应答已经获得了兴趣，因为基于HAdV的载体在基因治疗中的应用和在同种异体干细胞移植的儿科受者中的高感染率。由于抗病毒药物治疗往往是无效的，过继转移的选择HAdv-specific供体来源的T细胞在这些免疫功能低下的患者进行了调查。为了产生良好的生产实践相容的试剂，筛选了一组63个长的重叠的六邻体蛋白肽，以供T细胞识别。鉴定了5个30个氨基酸的保守肽，它们被大多数成年供体所识别。来自PBMC的长期培养物的CD 4（+）T细胞，用这组五种肽刺激，识别感染了属于不同物种的HAdV血清型的细胞。这些数据表明，成人T细胞优先识别HAdV结构蛋白的氨基酸残基的保守序列。在基因治疗的背景下，这一观察结果可能会限制切换到基于HAdV的载体的有益效果，该载体来源于不太常见的HAdV血清型，以试图规避预先存在的免疫力。然而，这种交叉反应性有利于HAdV特异性T细胞在免疫功能低下的移植受者中用于过继免疫治疗的应用。
The immune response against human adenovirus (HAdV) has gained interest because of the application of HAdV-based vectors in gene therapy and the high incidence of infections in pediatric recipients of allogeneic stem cell grafts. Because antiviral medication is frequently ineffective, the option of adoptive transfer of HAdv-specific donor-derived T cells in these immunocompromised patients is investigated. To generate good manufacturing practice-compatible reagents, a panel of 63 long, overlapping, peptides of the hexon protein was screened for recognition by T cells. Five conserved peptides of 30 amino acids were identified that were recognized by the majority of adult donors. CD4(+) T cells from long-term cultures of PBMC, stimulated with this set of five peptides, recognized cells infected with HAdV serotypes belonging to different species. These data demonstrate that adult human T cells preferentially recognize conserved sequences of amino acid residues from a structural protein of HAdV. In the context of gene therapy, this observation may limit the beneficial effect of switching to HAdV-based vectors derived from less common serotypes of HAdV in an attempt to circumvent pre-existing immunity. However, this cross-reactivity benefits the application of HAdV-specific T cells for adoptive immunotherapy in immunocompromised transplant recipients.