Increased detection of HIV-specific T cell responses by combination of central sequences with comparable immunogenicity
Increased detection of HIV-specific T cell responses by combination of central sequences with comparable immunogenicity
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DOI：
10.1097/qad.0b013e3282f42412
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发表时间：
2008-02-19
期刊：
影响因子：
3.8
通讯作者：
Brander, Christian
中科院分区：
文献类型：
--
作者：
Frahm, Nicole;Nickle, David C.;Brander, Christian
目的：评估感染HIV-1-M B和C分支的个体对来自B、C和M组序列的计算机设计的集中式HIV-1抗原的识别能力。方法：描述了三种集中序列--共识、祖先和树中心--每个集中序列都试图最小化与流行病毒的遗传距离。目前尚不清楚这些序列中是否有任何一种对T细胞识别具有优势。使用来自美国、秘鲁、巴巴多斯和南非的样本评估了B、C和M组集中多肽在ELISpot分析中的靶向能力。结果：每一组集中多肽在检测细胞毒性T细胞(CTL)反应方面都具有同等强大的能力。重要的是，这些组合检测到的反应要广泛得多。尽管在很少有序列通知这些集中序列的设计的群体中观察到了广泛的反应，但局部序列与各自测试集之间的遗传距离与应答率成反比。此外，在C分支感染者中，使用B分支多肽的CTL反应性相对于分支内肽反应降低，而对M群肽的反应与这些个体的分支内肽反应相当。结论：所有被测试的集中式抗原都提供了一套类似的有效抗原肽。然而，使用SET组合检测到的更广泛的反应突出了在疫苗制备中最大限度地覆盖HIV-1序列多样性的重要性，以及在评估HIV-1感染者和接种疫苗的人的CTL反应中的重要性。(C)2008年Wolters Kluwer Health I Lippincott Williams&Wilkins
Objective: To evaluate the recognition of computationally designed, centralized HIV-1 antigens derived from clade B, C and group M sequences by individuals infected with HIV-1 -M clades B and C.Methods: Three centralized sequences have been described - consensus, ancestor and center-of-tree - each of which attempts to minimize the genetic distance to circulating viruses. It is unclear whether any of these sequences affords an advantage for T cell recognition. The ability of centralized clade B and C and group M peptides to be targeted in ELISpot assays was assessed using samples from the United States, Peru, Barbados and South Africa.Results: Each of the clade-specific centralized peptide sets was equally powerful in detecting cytotoxic T cell (CTL) responses. Importantly, combination of these sets detected significantly broader responses. Although broad responses were observed in populations from which few sequences informed the design of these centralized sequences, the genetic distance between local sequences and the respective test set was inversely associated with response rates. Furthermore, the CTL reactivity in clade C-infected subjects using clade B peptides was reduced relative to within-clade peptide responses, while responses to group M peptides were comparable to within-clade peptide responses in these individuals.Conclusions: All tested centralized antigens provided a similarly potent set of antigenic peptides. However, the significantly broader responses detected using the combination of sets highlight the importance of maximizing coverage of HIV-1 sequence diversity in vaccine preparations, as well as in the evaluation of CTL responses in HIV-1-infected individuals and those vaccinated. (c) 2008 Wolters Kluwer Health I Lippincott Williams & Wilkins