Vaccination with an acidic polymerase, epitope of influenza virus elicits a potent antiviral T cell response but delayed clearance of an influenza virus challenge
Vaccination with an acidic polymerase, epitope of influenza virus elicits a potent antiviral T cell response but delayed clearance of an influenza virus challenge
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DOI：
10.4049/jimmunol.174.2.696
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发表时间：
2005-01-15
影响因子：
4.4
通讯作者：
Woodland, DL
中科院分区：
文献类型：
--
作者：
Crowe, SR;Miller, SC;Woodland, DL
表位选择的潜在机制和免疫优势等级对基于肽的疫苗的潜在影响还不清楚。最近，我们已经证明，两个免疫显性的MHC I类限制性表位，NP 366 -374 /D-h（核蛋白（NP））和PA（224-233）/D-h（酸性聚合酶（PA）），驱动CD 8（+）T细胞对流感病毒感染的C57 BL/6小鼠，在感染细胞上的差异表达。而NP似乎是强烈表达的所有感染的细胞，PA似乎是强烈表达的树突状细胞，但只有弱表达的非树突状细胞。因此，对流感病毒的免疫应答可能涉及对表位（如PA）特异的T细胞，所述表位在感染部位表达不足。为了检查差异Ag呈递对肽疫苗接种的后果，我们比较了用NP或PA肽疫苗接种的小鼠中T细胞应答和流感病毒清除的动力学。用NP或PA肽接种导致在流感病毒攻击后感染部位的Ag特异性T细胞应答加速和增强。这些T细胞在其产生IFN-γ和TNF-α以及介导细胞溶解活性的能力方面是完全功能性的。尽管这种增强的Ag特异性T细胞反应，PA疫苗接种流感病毒的清除有不利影响相比，未接种疫苗或NP接种的小鼠。这些数据表明，不同的Ag呈递影响T细胞对特定表位的应答的功效，并且这需要被考虑用于开发基于肽的疫苗接种策略。
The mechanisms underlying epitope selection and the potential impact of inummodominance hierarchies on peptide-based vaccines are not well understood. Recently, we have shown that two immumodominant MHC class I-restricted epitopes, NP366-374 /D-h (nucleoprotein (NP)) and PA(224-233)/D-h (acidic polymerase (PA)), which drive the CD8(+) T cell response to influenza virus infection in C57BL/6 mice, are differentially expressed on infected cells. Whereas NP appears to be strongly expressed on all infected cells, PA appears to be strongly expressed on dendritic cells but only weakly expressed on nondendritic cells. Thus, the immune response to influenza virus may involve T cells specific for epitopes, such as PA, that are poorly expressed it the site of infection. To examine the consequences of differential Ag presentation on peptide vaccination, we compared the kinetics of the T cell response and influenza virus clearance in mice vaccinated with the NP or PA peptide. Vaccination with either the NP or PA peptide resulted in accelerated and enhanced Ag-specific, T cell responses at the site of infection following influenza virus challenge. These T cells were fully functional in terms of their ability to produce IFN-gamma and TNF-alpha and to mediate cytolytic activity. Despite this enhancement of the Ag-specific T cell response, PA vaccination had a detrimental effect on the clearance of influenza virus compared with unvaccinated or NP-vaccinated mice. These data suggest that differential Ag presentation impacts the efficacy of T cell responses to, specific epitopes and that this needs to be considered for the development of peptide-based vaccination strategies.