Diverse recognition of conserved orthopoxvirus CD8+ T cell epitopes in vaccinated rhesus macaques.
Diverse recognition of conserved orthopoxvirus CD8+ T cell epitopes in vaccinated rhesus macaques.
复制标题
接种疫苗的恒河猴中保守的正痘病毒 CD8 T 细胞表位的多样化识别。
DOI：
10.1016/j.vaccine.2009.05.077
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发表时间：
2009
期刊：
影响因子：
5.5
通讯作者：
Johnson,RPaul
中科院分区：
文献类型：
--
作者：
Walsh,StephenR;Gillis,Jacqueline;Peters,Björn;Mothé,BiancaR;Sidney,John;Sette,Alessandro;Johnson,RPaul
牛痘病毒（VACV）诱导强烈的病毒特异性CD 8 + T细胞应答，其在控制痘病毒感染中起重要作用。为了鉴定免疫显性痘病毒蛋白并促进未来在非人灵长类动物中对天花疫苗的测试，我们使用了一种算法来预测能够与常见的猕猴MHC I类分子Mamu-A*01结合的VACV肽。我们合成了来自97个VACV ORF的294个肽;这些肽中的100个在Mamu-A*01结合基序的位置3处不包含典型的脯氨酸。通过IFNγ ELISPOT测定评估了两只接种牛痘疫苗的Mamu-A*01+猕猴PBMC中的细胞免疫应答。免疫猕猴识别17肽从16个不同的ORF与6肽识别的猕猴。与其他正痘病毒序列的比较显示，这些表位中有12个在VACV、天花和猴痘病毒之间是严格保守的。ELISPOT反应也观察到8个表位，不包含典型的P3脯氨酸。这些结果表明，病毒特异性CD 8 + T细胞应答广泛针对多种VACV蛋白，并且这些T细胞表位的子集在正痘病毒中高度保守。
Vaccinia virus (VACV) induces a vigorous virus-specific CD8+ T cell response that plays an important role in control of poxvirus infection. To identify immunodominant poxvirus proteins and to facilitate future testing of smallpox vaccines in non-human primates, we used an algorithm for the prediction of VACV peptides able to bind to the common macaque MHC class I molecule Mamu-A*01. We synthesized 294 peptides derived from 97 VACV ORFs; 100 of these peptides did not contain the canonical proline at position three of the Mamu-A*01 binding motif. Cellular immune responses in PBMC from two vaccinia-vaccinated Mamu-A*01+ macaques were assessed by IFNγ ELISPOT assays. Vaccinated macaques recognized 17 peptides from 16 different ORFs with 6 peptides recognized by both macaques. Comparison with other orthopoxvirus sequences revealed that 12 of these epitopes are strictly conserved between VACV, variola, and monkeypoxvirus. ELISPOT responses were also observed to eight epitopes that did not contain the canonical P3 proline. These results suggest that the virus-specific CD8+ T cell response is broadly directed against multiple VACV proteins and that a subset of these T cell epitopes is highly conserved among orthopoxviruses.