HLA Class I Binding of HBZ Determines Outcome in HTLV-1 Infection
HLA Class I Binding of HBZ Determines Outcome in HTLV-1 Infection
复制标题
DOI：
10.1371/journal.ppat.1001117
复制
发表时间：
2010-09-01
期刊：
影响因子：
6.7
通讯作者：
Asquith, Becca
中科院分区：
文献类型：
--
作者：
MacNamara, Aidan;Rowan, Aileen;Asquith, Becca
CD8(+) T细胞对病毒感染的宿主既有保护作用，也有有害作用。然而，目前还没有系统的方法来识别保护性CD8(+) T细胞反应的属性。在这里，我们结合理论和实验来确定和量化所有HLA I类等位基因对宿主抵抗特定病原体感染的贡献。在432例HTLV-1感染的个体中，我们发现具有强烈结合HTLV-1蛋白HBZ的HLA I类等位基因的个体具有较低的前病毒载量，并且更有可能无症状。我们还表明，一般来说，在所有HTLV-1蛋白中，CD8(+) T细胞的有效性在很大程度上取决于蛋白质特异性，并产生了从最有效的CD8(+) T细胞应答到最不有效的CD8(+) T细胞应答的蛋白质排序列表。我们得出结论，CD8(+) T细胞在HTLV-1的控制中起重要作用，并且HBZ特异性的CD8（+）细胞，而不是免疫优势蛋白Tax，是最有效的。我们认为HBZ在HTLV-1的持久性中起着核心作用。这种方法适用于所有病原体，即使在数据稀少的情况下，也可以同时识别HLA I类等位基因和负责保护性CD8(+) T细胞反应的表位。
CD8(+) T cells can exert both protective and harmful effects on the virus-infected host. However, there is no systematic method to identify the attributes of a protective CD8(+) T cell response. Here, we combine theory and experiment to identify and quantify the contribution of all HLA class I alleles to host protection against infection with a given pathogen. In 432 HTLV-1-infected individuals we show that individuals with HLA class I alleles that strongly bind the HTLV-1 protein HBZ had a lower proviral load and were more likely to be asymptomatic. We also show that in general, across all HTLV-1 proteins, CD8(+) T cell effectiveness is strongly determined by protein specificity and produce a ranked list of the proteins targeted by the most effective CD8(+) T cell response through to the least effective CD8(+) T cell response. We conclude that CD8(+) T cells play an important role in the control of HTLV-1 and that CD8(+) cells specific to HBZ, not the immunodominant protein Tax, are the most effective. We suggest that HBZ plays a central role in HTLV-1 persistence. This approach is applicable to all pathogens, even where data are sparse, to identify simultaneously the HLA Class I alleles and the epitopes responsible for a protective CD8(+) T cell response.