Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4(+) T cell depletion.
Targeting of conserved gag-epitopes in early HIV infection is associated with lower plasma viral load and slower CD4(+) T cell depletion.
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早期HIV感染中保守的gag表位的靶向与较低的血浆病毒载量和较慢的CD4(+)T细胞消耗有关。
DOI：
10.1089/aid.2012.0171
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发表时间：
2013
影响因子：
1.5
通讯作者：
Karlsson,AnnikaC
中科院分区：
文献类型：
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作者：
Perez,CarinaL;Milush,JeffreyM;Buggert,Marcus;Eriksson,EmilyM;Larsen,MetteV;Liegler,Teri;Hartogensis,Wendy;Bacchetti,Peter;Lund,Ole;Hecht,FrederickM;Nixon,DouglasF;Karlsson,AnnikaC
我们的目的是研究早期 HIV 感染中 CD8+T 细胞靶向的免疫显性 HIV-Gag 肽（可变或保守）的特征是否会影响 T 细胞反应的质量和数量，以及这是否会影响疾病进展的速度。旧金山加利福尼亚大学 OPTIONS 队列中未接受过治疗的 HIV 感染研究对象从感染后 44 天开始接受长达 6 年的监测。通过多色流式细胞术鉴定并表征了针对 HLA 匹配的 HIV-Gag 表位的 CD8+T 细胞反应。获得自体HIVgags序列。我们证明，在早期感染中针对保守的 HIV-Gag 表位的患者在整个研究期间维持了其表位特异性 CD8+T 细胞反应。尽管功能特征没有限制，但靶向可变表位的患者随着时间的推移表现出免疫反应下降，并且他们可能靶向其他可变表位。对保守表位的维持免疫反应与目标表位内没有或有限的序列进化相关。与针对可变表位的免疫反应患者相比，针对保守表位的免疫反应患者随着时间的推移，中位病毒载量显着较低（0.63log10差异）。此外，与针对可变表位的受试者（每月 1.85%）相比，针对保守表位的受试者（每月 0.85%）CD4+T 细胞下降速度更慢。先前的研究表明，基于特定 HLA 类型的抗原靶向与更好的病程相关。在这项研究中，我们证明根据表位的变异性对表位进行分类与临床结果相关。
We aimed to investigate whether the character of the immunodominant HIV-Gag peptide (variable or conserved) targeted by CD8+T cells in early HIV infection would influence the quality and quantity of T cell responses, and whether this would affect the rate of disease progression. Treatment-naive HIV-infected study subjects within the OPTIONS cohort at the University of California, San Francisco, were monitored from an estimated 44 days postinfection for up to 6 years. CD8+T cells responses targeting HLA-matched HIV-Gag-epitopes were identified and characterized by multicolor flow cytometry. The autologous HIVgagsequences were obtained. We demonstrate that patients targeting a conserved HIV-Gag-epitope in early infection maintained their epitope-specific CD8+T cell response throughout the study period. Patients targeting a variable epitope showed decreased immune responses over time, although there was no limitation of the functional profile, and they were likely to target additional variable epitopes. Maintained immune responses to conserved epitopes were associated with no or limited sequence evolution within the targeted epitope. Patients with immune responses targeting conserved epitopes had a significantly lower median viral load over time compared to patients with responses targeting a variable epitope (0.63 log10difference). Furthermore, the rate of CD4+T cell decline was slower for subjects targeting a conserved epitope (0.85% per month) compared to subjects targeting a variable epitope (1.85% per month). Previous studies have shown that targeting of antigens based on specific HLA types is associated with a better disease course. In this study we show that categorizing epitopes based on their variability is associated with clinical outcome.