Differential capacity of T cell priming in naive donors of promiscuous CD4+ T cell epitopes of HCVNS3 and Core proteins
Differential capacity of T cell priming in naive donors of promiscuous CD4+ T cell epitopes of HCVNS3 and Core proteins
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DOI：
10.1002/eji.200636783
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Maillere, Bernard
中科院分区：
文献类型：
--
作者：
Castelli, Florence A.;Leleu, Melanie;Maillere, Bernard
为了研究个体间和非病毒依赖性的CD 4（+）T细胞对HCV成分的反应的变异性，我们评估了HLA II分子对未感染的健康供体的这些反应的影响。使用HLA II特异性结合试验，我们确定，在核心和NS 3蛋白，21个长片段和24个15-mer肽，结合到4至8个最占优势的HLA II分子。然后，我们在12个HLA无关的健康供体中评估了8个长混杂肽的引发能力。NS 3 1250-1264肽在所有幼稚供体中引发T细胞，而其他五种肽在至少一半的个体中刺激。我们还报告了与多种HLA II分子结合但免疫原性较弱的序列。因此，我们得出结论：（i）广泛的HLA II特异性只是肽在多个个体中刺激的先决条件，（ii）混杂肽在引发未感染的健康供体的CD 4（+）T细胞的能力方面存在很大差异。我们认为，这些引发的差异导致个体间的肽特异性T细胞库的变化。有趣的是，我们鉴定的五种最具免疫原性的肽对应于感染患者中经常靶向的T细胞表位。
To process the inter-individual and virus-independent variability of CD4(+) T cell responses to HCV components, we evaluated the effect on these responses of HLA II molecules in uninfected healthy donars. Using HLA II-specific binding assays, we identified, in the Core and NS3 proteins, 21 long fragments and 24 15-mer peptides that bound to four to eight of the most preponderant HLA II molecules. We then evaluated the priming capacity of eight long promiscuous peptides in 12 HLA-unrelated healthy donors. The NS3 1250-1264 peptide primed T cells in all naive donors, while five others were stimulating in at least half of the individuals. We also report sequences that binds to multiple HLA II molecules but are weakly immunogenic. We therefore conclude that (i) broad HLA II specificity is only a prerequisite for a peptide to be stimulating in multiple individuals, and (ii) promiscuous peptides widely differ in their capacity to prime CD4(+) T cells from uninfected healthy donors. We suggest that these priming differences result from inter-individuals variations in the peptide-specific T cells repertoire. Interestingly, five of the most immunogenic peptides we identified correspond to frequently targeted T cell epitopes in infected patients.