Selective CD4+ T cell help for antibody responses to a large viral pathogen:: Deterministic linkage of specificities
Selective CD4+ T cell help for antibody responses to a large viral pathogen:: Deterministic linkage of specificities
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DOI：
10.1016/j.immuni.2008.04.018
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发表时间：
2008-06-01
期刊：
影响因子：
32.4
通讯作者：
Crotty, Shane
中科院分区：
文献类型：
--
作者：
Sette, Alessandro;Moutaftsi, Magdalini;Crotty, Shane
抗体反应是对许多病原体的保护性免疫反应的关键组成部分，但决定哪些蛋白质是目标的参数仍不清楚。使用单个 MHC-II 限制性痘苗病毒（VACV，天花疫苗）表位进行的疫苗接种显示，CD4（+）T 细胞对 B 细胞的帮助令人惊讶地不可转移到其他病毒体蛋白特异性。在针对抗体病毒体蛋白靶标的无偏筛选中鉴定出许多 VACV CD4(+) T 细胞反应，这与特异性之间的确定性联系一致。我们通过有效预测新的痘苗病毒 MHC II 表位（效率提高了 830%）来测试确定性连锁模型。最后，我们发现 CD4(+) T 细胞对于中和抗体的产生和体内保护性免疫的帮助是有限的。与标准模型相反，这些数据表明单个蛋白质是 B 细胞-T 细胞识别大型病毒的单位。因此，MHC 限制是抗病毒抗体反应的关键选择性事件，并且对于大型病原体的疫苗开发可能很重要。
Antibody responses are critical components of protective immune responses to many pathogens, but parameters determining which proteins are targeted remain unclear. Vaccination with individual MHC-II-restricted vaccinia virus (VACV, smallpox vaccine) epitopes revealed that CD4(+) T cell help to B cells was surprisingly nontransferable to other virion protein specificities. Many VACV CD4(+) T cell responses identified in an unbiased screen targeted antibody virion protein targets, consistent with deterministic linkage between specificities. We tested the deterministic linkage model by efficiently predicting new vaccinia MHC II epitopes (830% improved efficiency). Finally, we showed CD4(+) T cell help was limiting for neutralizing antibody development and protective immunity in vivo. In contrast to the standard model, these data indicate individual proteins are the unit of B cell-T cell recognition for a large virus. Therefore, MHC restriction is a key selective event for the antiviral antibody response and is probably important for vaccine development to large pathogens.