Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes
Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes
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DOI：
10.1038/ni1281
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发表时间：
2006-02-01
影响因子：
30.5
通讯作者：
Brander, C
中科院分区：
文献类型：
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作者：
Frahm, N;Kiepiela, P;Brander, C
尽管支持显性应答优于亚显性应答的数据有限，但免疫显性表位代表了优选的候选疫苗。为了阐明亚显性应答在人类免疫缺陷病毒感染中的作用，我们分析了受HLA-B *1503限制的细胞毒性T淋巴细胞应答，HLA-B *1503是一种在感染进化枝B的队列中罕见的等位基因，尽管在感染进化枝C的队列中常见。HLA-B *1503与进化枝B组群中病毒载量降低相关，但与进化枝C组群无关，尽管两者都具有免疫显性应答。进化枝B病毒控制与对几个亚显性细胞毒性T淋巴细胞表位的应答相关，而它们的进化枝C变体则不太被认可。这些数据表明，亚显性应答可有助于体内病毒控制，高HLA等位基因频率可驱动从循环病毒群体中消除亚显性但有效的表位。
Despite limited data supporting the superiority of dominant over subdominant responses, immunodominant epitopes represent the preferred vaccine candidates. To address the function of subdominant responses in human immunodeficiency virus infection, we analyzed cytotoxic T lymphocyte responses restricted by HLA-B*1503, a rare allele in a cohort infected with clade B, although common in one infected with clade C. HLA-B*1503 was associated with reduced viral loads in the clade B cohort but not the clade C cohort, although both shared the immunodominant response. Clade B viral control was associated with responses to several subdominant cytotoxic T lymphocyte epitopes, whereas their clade C variants were less well recognized. These data suggest that subdominant responses can contribute to in vivo viral control and that high HLA allele frequencies may drive the elimination of subdominant yet effective epitopes from circulating viral populations.