Long-term T cell memory to human leucocyte antigen-A2 supertype epitopes in humans vaccinated against smallpox
Long-term T cell memory to human leucocyte antigen-A2 supertype epitopes in humans vaccinated against smallpox
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DOI：
10.1111/j.1365-2249.2007.03401.x
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发表时间：
2007-08-01
影响因子：
4.6
通讯作者：
Kazura, J. W.
中科院分区：
文献类型：
--
作者：
Ostrout, N. D.;McHugh, M. M.;Kazura, J. W.
人类白细胞抗原（HLA）I类限制性T细胞表位的鉴定对于发展T细胞进化的追踪方法具有重要意义。新一代天花疫苗的记忆，并允许与已知诱导预防天花的旧牛痘病毒制剂进行比较。我们评估了四种计算算法的相对预测值，以确定候选9-mer HLA-A2超型表位，这些表位被证实优先刺激受试者27-54年前接种Dryvax疫苗的T细胞干扰素（IFN）-γ应答。14 L、G1 L、A8 R、I8 R、D12 L和H3 L编码的6个肽开放阅读框与牛痘病毒完全相同（哥本哈根），Variola major（Bangledesh 1975）和改良的牛痘安卡拉株相对于远程接种的非HLA-A2超型和未接种的HLA-A2超型，优先刺激27-49年前最后给予Dryvax的健康HLA-A2超型成人的IFN-γ应答。A2超型成人。组合来自使用不同策略来预测肽与HLA-A2超型分子结合的至少两种计算算法的结果对于通过回忆T细胞IFN-γ应答来确认为表位的候选肽的选择是最佳的。这些数据将有助于评价复制缺陷型天花疫苗（如改良安卡拉牛痘）的免疫原性，并有助于了解与长寿T细胞记忆相关的痘病毒表位。
Identification of human leucocyte antigen (HLA) class I-restricted T cell epitopes is important to develop methods to track the evolution of T cell. memory to new generation smallpox vaccines and allow comparison to older vaccinia virus preparations known to induce protection against smallpox. We evaluated the relative predictive values of four computational algorithms to identify candidate 9-mer HLA-A2 supertype epitopes that were confirmed to stimulate preferentially T cell interferon (IFN)-gamma responses by subjects last vaccinated with Dryvax 27-54 years previously. Six peptides encoded by 14L, G1L, A8R, I8R, D12L and H3L open reading frames that were identical for Vaccinia (Copenhagen), Variola major (Bangledesh 1975) and modified vaccinia Ankara strain preferentially stimulated IFN-gamma responses by healthy HLA-A2 supertype adults last given Dryvax 27-49 years earlier relative to remotely vaccinated non-HLA-A2 supertype and unvaccinated HLA-A2 supertype adults. Combining results from at least two computational algorithms that use different strategies to predict peptide binding to HLA-A2 supertype molecules was optimal for selection of candidate peptides that were confirmed to be epitopes by recall of T cell IFN-gamma responses. These data will facilitate evaluation of the immunogenicity of replication incompetent smallpox vaccines such as modified vaccinia Ankara and contribute to knowledge of poxvirus epitopes that are associated with long-lived T cell memory.