Conflicting hallmarks are attributed to cytomegalovirus (CMV) infections. CMVs are viewed as being master tacticians in “immune evasion” by subverting essentially all pathways of innate and adaptive immunity. On the other hand, CMV disease is undeniably restricted to the immunologically immature or immunocompromised host, whereas an intact immune system prevents virus spread, cytopathogenic tissue infection, and thus pathological organ manifestations. Therefore, the popular term “immune evasion” is apparently incongruous with the control of CMV infections in the immunocompetent human host as well as in experimental non-human primate and rodent models. Here, we review recent work from the mouse model that resolves this obvious discrepancy for the example of the virus-specific CD8 T-cell response. Immune evasion proteins encoded by murine CMV (mCMV) interfere with the cell surface trafficking of antigenic peptide-loaded MHC class-I (pMHC-I) complexes and thereby reduce their numbers available for interaction with T-cell receptors of CD8 T cells; but this inhibition is incomplete. As a consequence, while CD8 T cells with low interaction avidity fail to receive sufficient signaling for triggering their antiviral effector function in the presence of immune evasion proteins in infected cells, a few pMHC-I complexes that escape to the cell surface are sufficient for sensitizing high-avidity CD8 T cells. It is thus proposed that the function of immune evasion proteins is to raise the avidity threshold for activation, so that in the net result, only high-avidity cells can protect. An example showing that immune evasion proteins can make the difference between life and death is the lacking control of infection in a mouse model of MHC-I histoincompatible hematopoietic cell transplantation (allogeneic-HCT). In this model, only low-avidity CD8 T cells become reconstituted by HCT and almost all infected HCT recipients die of multiple-organ CMV disease when immune evasion proteins are expressed. In contrast, lowering the avidity threshold for antigen recognition by deletion of immune evasion proteins allowed control of infection and rescued from death.

相互矛盾的特征归因于巨细胞病毒 (CMV) 感染。CMV 被视为“免疫逃避”的战术大师，它基本上颠覆了先天免疫和适应性免疫的所有途径。另一方面，不可否认，CMV 疾病仅限于免疫不成熟或免疫功能低下的宿主，而完整的免疫系统可防止病毒传播、致细胞病变组织感染，从而防止病理器官表现。因此，流行的术语“免疫逃避”显然与免疫能力强的人类宿主以及实验性非人类灵长类动物和啮齿动物模型中 CMV 感染的控制不一致。在这里，我们回顾了小鼠模型最近的工作，该模型解决了病毒特异性 CD8 T 细胞反应示例的明显差异。由鼠 CMV (mCMV) 编码的免疫逃避蛋白会干扰抗原肽负载的 MHC I 类 (pMHC-I) 复合物的细胞表面运输，从而减少它们可用于与 CD8 T 细胞的 T 细胞受体相互作用的数量；但这种抑制是不完全的。因此，虽然具有低相互作用亲和力的 CD8 T 细胞在受感染细胞中存在免疫逃避蛋白的情况下无法接收到足够的信号以触发其抗病毒效应子功能，但一些逃逸到细胞表面的 pMHC-I 复合物足以致敏高亲和力 CD8 T 细胞。因此提出免疫逃避蛋白的功能是提高激活的亲和力阈值，因此在最终结果中，只有高亲和力细胞才能提供保护。MHC-I 组织不相容性造血细胞移植 (allogeneic-HCT) 小鼠模型缺乏对感染的控制，这表明免疫逃避蛋白可以决定生与死。在这个模型中，只有低亲和力的 CD8 T 细胞被 HCT 重组，几乎所有受感染的 HCT 接受者在表达免疫逃避蛋白时死于多器官 CMV 疾病。相反，通过删除免疫逃避蛋白来降低抗原识别的亲和力阈值可以控制感染并免于死亡。只有低亲和力的 CD8 T 细胞被 HCT 重组，几乎所有受感染的 HCT 受体在表达免疫逃避蛋白时死于多器官 CMV 疾病。相反，通过删除免疫逃避蛋白来降低抗原识别的亲和力阈值可以控制感染并免于死亡。只有低亲和力的 CD8 T 细胞被 HCT 重组，几乎所有受感染的 HCT 受体在表达免疫逃避蛋白时死于多器官 CMV 疾病。相反，通过删除免疫逃避蛋白来降低抗原识别的亲和力阈值可以控制感染并免于死亡。