Longitudinal Characterization of the Mumps-Specific HLA-A2 Restricted T-Cell Response after Mumps Virus Infection.

Longitudinal Characterization of the Mumps-Specific HLA-A2 Restricted T-Cell Response after Mumps Virus Infection.
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腮腺炎病毒感染后腮腺炎特异性HLA-A2的纵向表征限制了T细胞反应。

DOI:
10.3390/vaccines9121431
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发表时间:
2021-12-03
期刊:
影响因子:
7.8
通讯作者:
de Wit J
de Wit J
中科院分区:
医学3区
文献类型:
--
作者:
Lanfermeijer J;Nühn MM;Emmelot ME;Poelen MCM;van Els CACM;Borghans JAM;van Baarle D;Kaaijk P;de Wit J

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疫苗接种后腮腺炎病毒(MuV)特异性体液反应的减弱被认为是最近接种疫苗的年轻人发生腮腺炎疫情的原因,尽管它不能解释所有病例。此外,CD 8 + T细胞可能在针对MuV的应答中发挥重要作用;然而,关于MuV感染后MuV特异性CD 8 + T细胞应答的特征和动力学知之甚少。在这里,我们有机会在5个先前接种疫苗和3个未接种疫苗的个体中,从MuV感染后1.5至36个月,跟踪对最近鉴定的3个HLA-A2*02:01限制性MuV特异性表位的CD 8 + T细胞应答。感染诱导的CD 8 + T细胞应答主要由ALDQTDIRV和LLDSSTTRV表位特异性T细胞主导,而对GLMEGQIVSV表位的应答是亚显性的。血液中MuV特异性CD 8 + T细胞频率在感染后1.5至9个月之间下降。这种下降不能用抑制性受体或归巢标记物表达的变化来解释。尽管MuV特异性CD 8 + T细胞的频率和表型正在发生变化,但TCRβ分析显示随着时间的推移,MuV特异性T细胞库保持稳定。这些见解在维持对腮腺炎的细胞反应,可能会提供优化疫苗接种策略,以实现长期的细胞记忆反应的标志。
Waning of the mumps virus (MuV)-specific humoral response after vaccination has been suggested as a cause for recent mumps outbreaks in vaccinated young adults, although it cannot explain all cases. Moreover, CD8+ T cells may play an important role in the response against MuV; however, little is known about the characteristics and dynamics of the MuV-specific CD8+ T-cell response after MuV infection. Here, we had the opportunity to follow the CD8+ T-cell response to three recently identified HLA-A2*02:01-restricted MuV-specific epitopes from 1.5 to 36 months post-MuV infection in five previously vaccinated and three unvaccinated individuals. The infection-induced CD8+ T-cell response was dominated by T cells specific for the ALDQTDIRV and LLDSSTTRV epitopes, while the response to the GLMEGQIVSV epitope was subdominant. MuV-specific CD8+ T-cell frequencies in the blood declined between 1.5 and 9 months after infection. This decline was not explained by changes in the expression of inhibitory receptors or homing markers. Despite the ongoing changes in the frequencies and phenotype of MuV-specific CD8+ T cells, TCRβ analyses revealed a stable MuV-specific T-cell repertoire over time. These insights in the maintenance of the cellular response against mumps may provide hallmarks for optimizing vaccination strategies towards a long-term cellular memory response.
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