Cell Type-Specific Proteasomal Processing of HIV-1 Gag-p24 Results in an Altered Epitope Repertoire
Cell Type-Specific Proteasomal Processing of HIV-1 Gag-p24 Results in an Altered Epitope Repertoire
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HIV-1 Gag-p24 的细胞类型特异性蛋白酶体加工导致表位库改变
DOI：
10.1128/jvi.01790-10
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发表时间：
2010
影响因子：
5.4
通讯作者：
M. Rao
中科院分区：
文献类型：
--
作者：
N. Steers;J. Currier;G. Kijak;Robert C. di Targiani;A. Saxena;M. Marovich;Jerome H. Kim;N. Michael;C. Alving;M. Rao
摘要蛋白酶体是通过主要组织相容性复合体（MHC）I类途径加工抗原的关键。HIV-1 Gag蛋白是几种实验性HIV-1疫苗的组分。因此，了解HIV-1 Gag蛋白的加工过程及其产生的表位库至关重要。使用来自同一志愿者的成熟树突状细胞（DC）和活化的CD 4 + T细胞的纯化蛋白酶体切割全长Gag-p24蛋白，并通过质谱法鉴定所得肽片段。不同的蛋白酶体降解模式和肽片段是成熟DC或活化的CD 4 + T细胞所特有的。产生的肽几乎一半是细胞类型特异性的。在从两种细胞类型鉴定的肽中观察到两个额外的差异。这些在HLA-B35-Px表位和HLA-B27-KK 10表位中。这些表位与HIV-1疾病进展有关。我们的研究结果表明，前体MHC I类表位的产生来源可能是诱导相关表位特异性细胞毒性T细胞的关键因素。
ABSTRACT Proteasomes are critical for the processing of antigens for presentation through the major histocompatibility complex (MHC) class I pathway. HIV-1 Gag protein is a component of several experimental HIV-1 vaccines. Therefore, understanding the processing of HIV-1 Gag protein and the resulting epitope repertoire is essential. Purified proteasomes from mature dendritic cells (DC) and activated CD4+ T cells from the same volunteer were used to cleave full-length Gag-p24 protein, and the resulting peptide fragments were identified by mass spectrometry. Distinct proteasomal degradation patterns and peptide fragments were unique to either mature DC or activated CD4+ T cells. Almost half of the peptides generated were cell type specific. Two additional differences were observed in the peptides identified from the two cell types. These were in the HLA-B35-Px epitope and the HLA-B27-KK10 epitope. These epitopes have been linked to HIV-1 disease progression. Our results suggest that the source of generation of precursor MHC class I epitopes may be a critical factor for the induction of relevant epitope-specific cytotoxic T cells.
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影响因子：
158.5
作者：
Gao, XJ;Nelson, GW;Carrington, M
通讯作者：
Carrington, M
影响因子：
56.9
作者：
Carrington, M;Nelson, GW;O'Brien, SJ
通讯作者：
O'Brien, SJ
DOI：
10.1073/pnas.0408773102
发表时间：
2005-03-22
影响因子：
11.1
作者：
Betts, MR;Exley, B;Ferrari, G
通讯作者：
Ferrari, G
DOI：
10.1073/pnas.91.20.9213
发表时间：
1994-09-27
影响因子：
11.1
作者：
GACZYNSKA, M;ROCK, KL;GOLDBERG, AL
通讯作者：
GOLDBERG, AL