Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
J Clin Invest. 2010 Jun;120(6):1885-94. doi: 10.1172/JCI41538. Epub 2010 May 3.
CD8+ T cell responses to viral infection are characterized by the emergence of dominant and subdominant CTL populations. The immunodominance hierarchies of these populations are highly reproducible for any given spectrum of virus-induced peptide-MHCI complexes and are likely determined by multiple factors. Recent studies demonstrate a direct correlation between naive epitope-specific CD8+ T cell precursor (CTLp) frequency and the magnitude of the response after antigen challenge. Thus, the number of available precursors in the naive pool has emerged as a key predictor of immunodominance. In contrast to this, we report here no consistent relationship between CTLp frequency and the subsequent magnitude of the immune response for 4 influenza virus-derived epitopes following intranasal infection of mice with influenza A virus. Rather, the characteristic, antigen-driven T cell immunodominance hierarchy was determined by the extent of recruitment from the available pool of epitope-specific precursors and the duration of their continued expansion over the course of the infection. These findings suggest possibilities for enhancing protective immune memory by maximizing both the size and diversity of typically subdominant T cell responses through rational vaccine design.
CD8+ T 细胞对病毒感染的反应表现为主要和次要 CTL 群体的出现。对于任何特定的病毒诱导的肽-MHC I 复合物谱,这些群体的免疫优势层次结构具有高度的重现性,并且可能由多种因素决定。最近的研究表明,幼稚表位特异性 CD8+ T 细胞前体 (CTLp) 的频率与抗原挑战后的反应强度之间存在直接相关性。因此,在幼稚池中可用的前体数量已成为免疫优势的关键预测因素。与此相反,我们在这里报告了在通过鼻内感染流感病毒后,针对 4 个流感病毒衍生表位,CTLp 频率与随后的免疫反应强度之间没有一致的关系。相反,特征性的、抗原驱动的 T 细胞免疫优势层次结构是由可用的表位特异性前体池中招募的程度以及它们在感染过程中持续扩展的时间决定的。这些发现表明,通过合理的疫苗设计,最大程度地增加通常次要的 T 细胞反应的大小和多样性,从而增强保护性免疫记忆是可能的。
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