Processing of recombinant Listeria monocytogenes proteins for MHC class I presentation follows a dedicated, high-efficiency pathway.
Processing of recombinant Listeria monocytogenes proteins for MHC class I presentation follows a dedicated, high-efficiency pathway.
复制标题
DOI：
10.4049/jimmunol.1201660
复制
发表时间：
2013-03-15
期刊：
影响因子：
--
通讯作者：
Princiotta MF
中科院分区：
文献类型：
--
作者：
Wolf BJ;Princiotta MF
CD8+T淋巴细胞识别与抗原提呈细胞表面MHC-I类分子(PMHC)结合的8-10个氨基酸的短肽。这些多肽既可以由呈递细胞的生物合成机制合成的内源蛋白产生，也可以由外源蛋白产生。由于大部分关于MHC I类加工途径的研究都集中在内源合成的蛋白质上，因此尚不清楚内源合成的蛋白质与外源的蛋白质所遵循的加工途径是否存在差异。为了突出内源蛋白和外源蛋白在加工过程中的潜在差异，我们开发了一个模型系统来衡量从痘苗病毒和单核细胞增生性李斯特菌表达的几乎相同的重组蛋白产生pMHC的效率。在这些实验中，我们发现，与内源性合成的病毒蛋白相比，重组李斯特菌抗原的处理和呈递方式有显著不同。具体地说，我们发现，从分泌的李斯特菌蛋白中产生pMHC的速度是相同的，与其来源的蛋白质的细胞半衰期无关，而从内源合成的病毒蛋白中产生pMHC的速度绝对取决于其蛋白质的半衰期。因此，我们的数据表明，存在一种独特而高效的MHC I类递呈途径，用于处理至少一些外源合成的蛋白质。
CD8+ T lymphocytes recognize short peptides of ~8–10 amino acids bound to MHC class I molecules (pMHC) on the surface of antigen presenting cells. These peptides can be generated from either endogenous proteins synthesized by the biosynthetic machinery of the presenting cell or from exogenously sourced proteins. Because much of the research characterizing the MHC class I processing pathway has focused on endogenously synthesized proteins, it is not known whether differences exist in the processing pathway followed by endogenously synthesized versus exogenously sourced proteins. To highlight potential differences in the processing of endogenous versus exogenous proteins, we developed a model system to measure the efficiency of pMHC generation from nearly identical recombinant proteins expressed from vaccinia virus and Listeria monocytogenes. In these experiments, we uncovered a striking difference in the way recombinant Listeria antigens are processed and presented when compared to endogenously synthesized viral proteins. Specifically, we find that pMHC production from secreted Listeria proteins occurs at the same rate, independent of the cellular half-life of the protein from which it is derived, whereas the rate of pMHC production from endogenously synthesized viral proteins is absolutely dependent on its protein half-life. Accordingly, our data demonstrate the existence of a distinct and highly efficient MHC class I presentation pathway used for the processing of at least some exogenously synthesized proteins.
登录
查看更多内容
影响因子：
16.8
作者：
Yewdell JW
通讯作者：
Yewdell JW
影响因子：
3.1
作者：
Moors, MA;Levitt, B;Portnoy, DA
通讯作者：
Portnoy, DA
影响因子：
32.4
作者：
Porgador, A;Yewdell, JW;Germain, RN
通讯作者：
Germain, RN
影响因子：
2.8
作者：
Miner, Maurine D.;Port, Gary C.;Freitag, Nancy E.
通讯作者：
Freitag, Nancy E.
影响因子：
32.4
作者：
Princiotta, MF;Finzi, D;Yewdell, JW
通讯作者：
Yewdell, JW