An unbiased peptide-wide discovery approach to select Mycobacterium tuberculosis antigens that target CD8+ T cell response during infection.
An unbiased peptide-wide discovery approach to select Mycobacterium tuberculosis antigens that target CD8+ T cell response during infection.
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DOI：
10.1016/j.vaccine.2013.07.077
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发表时间：
2013-10-01
期刊：
影响因子：
5.5
通讯作者：
Campos-Neto, Antonio
中科院分区：
文献类型：
--
作者：
Cayabyab, Mark J.;Qin, Lizeng;Kashino, Suely S.;Izzo, Angelo;Campos-Neto, Antonio
越来越多的数据强烈支持CD 8 + T细胞在抗结核免疫中的可能作用。因此，非常需要针对结核分枝杆菌（Mtb）的多价疫苗，其将CD 8 + T细胞抗原与引发CD 4 + T细胞的抗原结合。为了筛选潜在的CD 8 + T细胞抗原，在感染过程中产生的结核分枝杆菌，我们分离病原体衍生的肽，结合MHC I类分子表达的粘附脾细胞从结核分枝杆菌感染的小鼠。质谱分析揭示了以下四种与Mtb蛋白具有100%同源性的九聚体肽：DGYVGAPAH（MT_0401）、TTMPLFAD（MT_1164）、RSGAATPVR（MT_2160.1）和LAAVVGVVL（MT_0078）。MT_0401基因编码5′-磷酸核糖基甘氨酰胺转化酶2蛋白，其他3个基因编码功能未知的假定蛋白。NCBI/Blast分析显示，在四种肽中，DGYVGAPAH具有最高的最大比对得分和最低的E值（偶然预期的比对数目）。因此，我们评估了在两种基因疫苗制剂中表达的MT_0401是否能够刺激对DGYVGAPAH肽特异性的CD 8 + T细胞应答。当用重组质粒DNA和表达MT 0401蛋白的E1/E3缺失的腺病毒5免疫小鼠时，使用同源和异源初免-加强方案，它们产生了对全长MT 0401蛋白的强DGYVGAPAH特异性CD 8 + T细胞应答以及抗体和CD 4+特异性T细胞应答。同样重要的是观察到感染Mtb的小鼠在脾和肺中均产生DGYVGAPAH特异性CD 8 + T细胞应答。这些结果表明，通过MHC I类机器加工和呈递的Mtb抗原可以通过所述方法容易地鉴定，并且可以是有用的候选抗原以刺激疫苗开发程序中的特异性CD 8 + T细胞应答。
Accruing data strongly support the possible role of CD8+ T cells in immunity against tuberculosis (TB). Multivalent vaccines against Mycobacterium tuberculosis (Mtb) that incorporate CD8+ T cell antigens with those that elicit CD4+ T cells are therefore highly desirable. To screen for potential CD8+ T cell antigens that are produced by Mtb during infection, we isolated pathogen-derived peptides that bound to MHC Class I molecules expressed in adherent splenocytes obtained from Mtb-infected mice. Mass spectroscopy analysis revealed the following four nonamer peptides that had 100% homology with Mtb proteins: DGYVGAPAH (MT_0401), TTMPLFAD (MT_1164), RSGAATPVR (MT_2160.1) and LAAVVGVVL (MT_0078). The gene MT_0401 codes the protein 5′-Phosphoribosylglycinamide transformylase 2 and the other three genes code for hypothetical proteins with unknown function. The NCBI/Blast analysis showed that among the four peptides DGYVGAPAH had the highest maximum alignment score and lowest E value (number of alignments expected by chance). Therefore, we assessed whether MT_0401 expressed in two genetic vaccine formulations was capable of stimulating CD8+ T cell response that is specific to DGYVGAPAH peptide. When mice were immunized with a recombinant plasmid DNA and an E1/E3-deleted Adenovirus 5 expressing MT0401 protein, using both homologous and heterologous prime-boost protocols, they developed strong DGYVGAPAH-specific CD8+ T cell response as well as antibody and CD4+ specific T cell response to the full length MT0401 protein. Equally important was the observation that mice infected with Mtb developed DGYVGAPAH-specific CD8+ T cell responses in both spleen and lungs. These results demonstrate that Mtb antigens that are processed and presented via MHC Class I machinery can be readily identified by the described approach and may be useful candidate antigens to stimulate specific CD8+ T cell responses in vaccine development programs.
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促进全身自身免疫性B细胞成熟的T细胞。
影响因子：
8.7
作者：
Weinstein JS;Hernandez SG;Craft J
通讯作者：
Craft J
DOI：
10.4049/jimmunol.1200061
发表时间：
2013-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Green AM;Difazio R;Flynn JL
通讯作者：
Flynn JL
影响因子：
6
作者：
Kashino, Suely S.;Vallerskog, Therese;Campos-Neto, Antonio
通讯作者：
Campos-Neto, Antonio
影响因子：
4.4
作者：
Mukherjee, S;Kashino, SS;Campos-Neto, A
通讯作者：
Campos-Neto, A
影响因子：
4.4
作者：
Billeskov, Rolf;Vingsbo-Lundberg, Carina;Dietrich, Jes
通讯作者：
Dietrich, Jes