Identification of cryptic MHC I-restricted epitopes encoded by HIV-1 alternative reading frames.

Identification of cryptic MHC I-restricted epitopes encoded by HIV-1 alternative reading frames.
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DOI:
10.1084/jem.20031869
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发表时间:
2004-04-19
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Habel A
Habel A
中科院分区:
其他
文献类型:
--
作者:
Cardinaud S;Moris A;Février M;Rohrlich PS;Weiss L;Langlade-Demoyen P;Lemonnier FA;Schwartz O;Habel A

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人类免疫缺陷病毒(HIV)1主要组织相容性复合体(MHC)I限制性表位被广泛认为来源于由初级开放阅读框编码的病毒蛋白。然而,HIV-1基因组包含可能编码小分子多肽的替代阅读框架(ARF)。我们已经确定了一组由gag、pol和env基因内的ARF编码的表位。相应的表位多肽在人源化MHC-I分子的小鼠中具有免疫原性。此外,在HIV感染患者中还发现了识别这些表位的细胞毒性T淋巴细胞。这些结果揭示了HIV-1表位产生的非典型机制的存在。它们表明,细胞抗HIV-1免疫反应识别的表位范围比最初认为的要广泛。在设计旨在激活这些反应的疫苗策略时,应考虑到这一点。
Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I–restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides. We have identified a panel of epitopes encoded by ARFs within the gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes recognizing these epitopes were found in HIV-infected patients. These results reveal the existence of atypical mechanisms of HIV-1 epitope generation. They indicate that the repertoire of epitopes recognized by the cellular anti–HIV-1 immune response is broader than initially thought. This should be taken into account when designing vaccine strategies aimed at activating these responses.
DOI: 10.1083/jcb.108.2.229
发表时间: 1989-02
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