Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition by cytotoxic CD8⁺ T cells (CTLs), which is well-illustrated by our prior studies on cowpox virus (CPXV) that encodes potent MHCI inhibitors. Deletion of CPXV viral MHCI inhibitors markedly attenuated in vivo infection due to effects on CTL effector function, not priming. However, the CTL response to CPXV in C57BL/6 mice is dominated by a single peptide antigen presented by H-2K^b. Here we evaluated the effect of viral MHCI inhibition on immunodominant (IDE) and subdominant epitopes (SDE) as this has not been thoroughly examined. We found that cross-priming, but not cross-dressing, is the main mechanism driving IDE and SDE CTL responses following CPXV infection. Secretion of the immunodominant antigen was not required for immunodominance. Instead, immunodominance was caused by CTL interference, known as immunodomination. Both immunodomination and cross-priming of SDEs were not affected by MHCI inhibition. SDE-specific CTLs were also capable of exerting immunodomination during primary and secondary responses, which was in part dependent on antigen abundance. Furthermore, CTL responses directed solely against SDEs protected against lethal CPXV infection, but only in the absence of the CPXV MHCI inhibitors. Thus, both SDE and IDE responses can contribute to protective immunity against poxviruses, implying that these principles apply to poxvirus-based vaccines.

病毒已经进化出抑制MHCI的机制，从而逃避了细胞毒性CD8 ⁺ T细胞（CTL）的识别，这在我们先前对编码有效MHCI抑制剂的牛痘病毒（CPXV）的研究中得到了很好的说明。由于对CTL效应子功能的影响而不是启动，CPXV病毒MHCI抑制剂的删除显着减轻了体内感染。但是，C57BL / 6小鼠对CPXV的CTL反应主要由H-2K ^b呈递的单个肽抗原控制。在这里，我们评估了病毒MHCI抑制对免疫显性（IDE）和显性表位（SDE）的影响，因为尚未对此进行全面检查。我们发现交叉引发而不是交叉修饰是CPXV感染后驱动IDE和SDE CTL响应的主要机制。免疫优势不需要分泌免疫优势抗原。相反，免疫优势是由CTL干扰引起的，称为免疫优势。SDE的免疫控制和交叉引发均不受MHCI抑制的影响。SDE特异的CTL还能在主要和次要反应中发挥免疫作用，这部分取决于抗原的丰度。此外，仅针对SDE的CTL应答可防止CPXV致死性感染，但仅在CPXV MHCI抑制剂不存在的情况下才如此。因此，