Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
J Immunol. 2013 Mar 15;190(6):2501-9. doi: 10.4049/jimmunol.1201660. Epub 2013 Feb 8.
CD8(+) T lymphocytes recognize short peptides of ∼8-10 aa bound to MHC class I molecules (pMHC) on the surface of APCs. 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 Ags are processed and presented when compared with 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.
CD8(+) T 淋巴细胞识别与 APC 表面 MHC Ⅰ类分子结合的约 8-10 个氨基酸的短肽（pMHC）。这些肽可以来自呈递细胞生物合成机制合成的内源性蛋白，也可以来自外源性蛋白。由于大多数表征 MHCⅠ类加工途径的研究都集中在内源性合成蛋白上，因此尚不清楚内源性合成蛋白与外源性蛋白的加工途径是否存在差异。为了突出内源性蛋白与外源性蛋白加工的潜在差异，我们开发了一种模型系统，以测量来自痘苗病毒和李斯特菌的几乎相同重组蛋白的 pMHC 生成效率。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加工和呈递方式存在显著差异。具体而言，我们发现，无论其来源蛋白的细胞半衰期如何，分泌的李斯特菌蛋白的 pMHC 产生速率相同，而内源性合成的病毒蛋白的 pMHC 产生速率则完全取决于其蛋白半衰期。因此，我们的数据表明，至少某些外源性合成蛋白的加工存在一种独特且高效的 MHCⅠ类呈递途径。
