Data from: Epitope-specific CD8+ T cell kinetics rather than viral variability determine the timing of immune escape in Simian Immunodeficiency Virus infection

CD8+ T cells are important for the control of chronic HIV infection. However, the virus rapidly acquires “escape mutations” that reduce CD8+ T cell recognition and viral control. The timing of when immune escape occurs at a given epitope varies widely among patients and also among different epitopes within a patient. The strength of the CD8+ T cell response, as well as mutation rates, patterns of particular amino acids undergoing escape, and growth rates of escape mutants, may affect when escape occurs. In this study, we analyze the epitope-specific CD8+ T cells in 25 SIV-infected pigtail macaques responding to three SIV epitopes. Two epitopes showed a variable escape pattern and one had a highly monomorphic escape pattern. Despite very different patterns, immune escape occurs with a similar delay of on average 18 d after the epitope-specific CD8+ T cells reach 0.5% of total CD8+ T cells. We find that the most delayed escape occurs in one of the highly variable epitopes, and that this is associated with a delay in the epitope-specific CD8+ T cells responding to this epitope. When we analyzed the kinetics of immune escape, we found that multiple escape mutants emerge simultaneously during the escape, implying that a diverse population of potential escape mutants is present during immune selection. Our results suggest that the conservation or variability of an epitope does not appear to affect the timing of immune escape in SIV. Instead, timing of escape is largely determined by the kinetics of epitope-specific CD8+ T cells.

CD8阳性T细胞（CD8+ T cells）对于慢性HIV感染的控制发挥关键作用。然而，病毒会快速获得逃逸突变（escape mutations），以降低CD8阳性T细胞的识别效率与病毒控制效果。在不同患者群体中，乃至同一患者体内的不同表位（epitope）之间，免疫逃逸发生于特定表位的时机存在显著差异。CD8阳性T细胞的应答强度、突变率、发生逃逸的特定氨基酸模式，以及逃逸突变株的生长速率，均可能对逃逸发生的时机产生影响。

本研究对25只感染猴免疫缺陷病毒（SIV）的猪尾猕猴体内的表位特异性CD8阳性T细胞展开分析，这些细胞针对3种猴免疫缺陷病毒表位产生应答。其中2种表位呈现可变逃逸模式，剩余1种表位则呈现高度单型的逃逸模式。尽管逃逸模式差异显著，但当表位特异性CD8阳性T细胞占总CD8阳性T细胞比例达到0.5%时，免疫逃逸的平均发生延迟时长均约为18天。

本研究发现，逃逸发生最延迟的案例出现在1种高变异性表位中，且该现象与表位特异性CD8阳性T细胞针对该表位产生应答的延迟存在关联。通过分析免疫逃逸的动力学（kinetics）特征，我们发现逃逸过程中会同时涌现多种逃逸突变株，这提示在免疫选择压力下，宿主体内存在多样化的潜在逃逸突变株种群。

研究结果表明，表位的保守性或变异性似乎并不会影响猴免疫缺陷病毒感染模型中的免疫逃逸发生时机；相反，逃逸时机主要由表位特异性CD8阳性T细胞的应答动力学所决定。