The MHC class I peptide repertoire is molded by the transcriptome.
The MHC class I peptide repertoire is molded by the transcriptome.
复制标题
DOI：
10.1084/jem.20071985
复制
发表时间：
2008-03-17
期刊：
影响因子：
--
通讯作者：
Thibault P
中科院分区：
文献类型：
--
作者：
Fortier MH;Caron E;Hardy MP;Voisin G;Lemieux S;Perreault C;Thibault P
在稳态条件下，主要组织相容性复合体（MHC）I分子与自身肽相关，这些肽统称为MHC I类肽（MIP）库。很少有人知道的MIP剧目的起源和分子组成。我们开发了一种新的高通量质谱方法，产生一个准确的定义的性质和相对丰度的未标记的肽提出的MHC I分子。我们确定了189和196 MHC I相关肽正常和肿瘤小鼠胸腺细胞，分别。通过整合我们的肽组数据与转录组的全局分析，我们得出了两个结论。原代小鼠胸腺细胞的MIP库偏向于来自高度丰富的转录本的肽，并且富含来自细胞周期蛋白/细胞周期蛋白依赖性激酶和解旋酶的肽。此外，我们发现，大约25%的MHC I相关肽的差异表达对正常与肿瘤胸腺细胞。这些肽中约有一半来源于直接参与肿瘤转化的分子（例如，PI 3 K-AKT-mTOR通路的组分）。在大多数情况下，癌细胞上MHC I肽的过表达需要转录后机制。我们的研究结果表明，高通量分析和测序的MHC I相关肽产生独特的见解MIP剧目在正常和肿瘤细胞的起源。
Under steady-state conditions, major histocompatibility complex (MHC) I molecules are associated with self-peptides that are collectively referred to as the MHC class I peptide (MIP) repertoire. Very little is known about the genesis and molecular composition of the MIP repertoire. We developed a novel high-throughput mass spectrometry approach that yields an accurate definition of the nature and relative abundance of unlabeled peptides presented by MHC I molecules. We identified 189 and 196 MHC I–associated peptides from normal and neoplastic mouse thymocytes, respectively. By integrating our peptidomic data with global profiling of the transcriptome, we reached two conclusions. The MIP repertoire of primary mouse thymocytes is biased toward peptides derived from highly abundant transcripts and is enriched in peptides derived from cyclins/cyclin-dependent kinases and helicases. Furthermore, we found that ∼25% of MHC I–associated peptides were differentially expressed on normal versus neoplastic thymocytes. Approximately half of those peptides are derived from molecules directly implicated in neoplastic transformation (e.g., components of the PI3K–AKT–mTOR pathway). In most cases, overexpression of MHC I peptides on cancer cells entailed posttranscriptional mechanisms. Our results show that high-throughput analysis and sequencing of MHC I–associated peptides yields unique insights into the genesis of the MIP repertoire in normal and neoplastic cells.
登录
查看更多内容
影响因子：
20.3
作者：
Dorn, Tatjana;Kuhn, Ursula;Brakebusch, Cord
通讯作者：
Brakebusch, Cord
影响因子：
20.3
作者：
Jedema, I;van der Werff, NM;Falkenburg, JHF
通讯作者：
Falkenburg, JHF
影响因子：
4.4
作者：
Hickman, HD;Luis, AD;Hildebrand, WH
通讯作者：
Hildebrand, WH
影响因子：
64.5
作者：
ALDRICH, CJ;DECLOUX, A;FORMAN, J
通讯作者：
FORMAN, J
影响因子：
56.9
作者：
HUNT, DF;HENDERSON, RA;ENGELHARD, VH
通讯作者：
ENGELHARD, VH