Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage.
Characterization of HIV-specific CD4+ T cell responses against peptides selected with broad population and pathogen coverage.
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DOI：
10.1371/journal.pone.0039874
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Karlsson AC
中科院分区：
文献类型：
--
作者：
Buggert M;Norström MM;Czarnecki C;Tupin E;Luo M;Gyllensten K;Sönnerborg A;Lundegaard C;Lund O;Nielsen M;Karlsson AC
CD 4 + T细胞协调针对病毒感染的免疫，但它们在HIV感染中的重要性仍然存在争议。然而，全面的研究表明，HIV特异性CD 4 + T细胞的宽度和功能特性的增加与病毒载量的降低有关。在具有不同种族背景的人群中鉴定靶向广泛反应性表位的HIV特异性CD 4 + T细胞的主要挑战源于HIV的巨大基因组变异和宿主细胞免疫系统的多样性。在这里，我们描述了一种新的表位选择策略，PopCover，旨在解决这一挑战，并确定一组潜在的HLA II类限制性HIV表位，在演唱会上将提供最佳的病毒和宿主的覆盖。使用这种选择策略，我们鉴定了位于HIV的Gag、Nef、Env、Pol和达特蛋白区域中的64个推定表位（肽）。总的来说，发现73%的预测肽诱导HIV特异性CD 4 + T细胞应答。Gag和Nef肽诱导大多数反应。绝大多数肽（93%）预测限制患者的HLA等位基因。有趣的是，病毒血症患者的病毒载量与靶向Gag肽的数量呈负相关。此外，发现预测的Gag肽与常用的Gag-p55肽库相比诱导更广泛的多功能CD 4 + T细胞应答。这些结果证明了PopCover方法用于鉴定广泛认可的HLA II类限制性表位的能力。总之，选择策略，如PopCover，可能会成功地用于评估抗原特异性CD 4 + T细胞应答和设计未来的疫苗。
CD4+ T cells orchestrate immunity against viral infections, but their importance in HIV infection remains controversial. Nevertheless, comprehensive studies have associated increase in breadth and functional characteristics of HIV-specific CD4+ T cells with decreased viral load. A major challenge for the identification of HIV-specific CD4+ T cells targeting broadly reactive epitopes in populations with diverse ethnic background stems from the vast genomic variation of HIV and the diversity of the host cellular immune system. Here, we describe a novel epitope selection strategy, PopCover, that aims to resolve this challenge, and identify a set of potential HLA class II-restricted HIV epitopes that in concert will provide optimal viral and host coverage. Using this selection strategy, we identified 64 putative epitopes (peptides) located in the Gag, Nef, Env, Pol and Tat protein regions of HIV. In total, 73% of the predicted peptides were found to induce HIV-specific CD4+ T cell responses. The Gag and Nef peptides induced most responses. The vast majority of the peptides (93%) had predicted restriction to the patient’s HLA alleles. Interestingly, the viral load in viremic patients was inversely correlated to the number of targeted Gag peptides. In addition, the predicted Gag peptides were found to induce broader polyfunctional CD4+ T cell responses compared to the commonly used Gag-p55 peptide pool. These results demonstrate the power of the PopCover method for the identification of broadly recognized HLA class II-restricted epitopes. All together, selection strategies, such as PopCover, might with success be used for the evaluation of antigen-specific CD4+ T cell responses and design of future vaccines.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.3
作者：
Nielsen M;Lundegaard C;Blicher T;Peters B;Sette A;Justesen S;Buus S;Lund O
通讯作者：
Lund O
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
82.9
作者：
Fischer, Will;Perkins, Simon;Korber, Bette T.
通讯作者：
Korber, Bette T.
影响因子：
4.4
作者：
Hoof, Ilka;Perez, Carina L.;Karlsson, Annika C.
通讯作者：
Karlsson, Annika C.