Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2012 May 1;109(18):7025-30. doi: 10.1073/pnas.1112387109. Epub 2012 Apr 16.
To better understand the generation of MHC class I-associated peptides, we used a model antigenic protein whose proteasome-mediated degradation is rapidly and reversibly controlled by Shield-1, a cell-permeant drug. When expressed from a stably transfected gene, the efficiency of antigen presentation is ~2%, that is, one cell-surface MHC class I-peptide complex is generated for every 50 folded source proteins degraded upon Shield-1 withdrawal. By contrast, when the same protein is expressed by vaccinia virus, its antigen presentation efficiency is reduced ~10-fold to values similar to those reported for other vaccinia virus-encoded model antigens. Virus infection per se does not modify the efficiency of antigen processing. Rather, the efficiency difference between cellular and virus-encoded antigens is based on whether the antigen is synthesized from transgene- vs. virus-encoded mRNA. Thus, class I antigen-processing machinery can distinguish folded proteins based on the precise details of their synthesis to modulate antigen presentation efficiency.
为了更好地理解 MHC I 类相关肽的产生，我们使用了一种模型抗原蛋白，其蛋白酶体介导的降解可被 Shield-1 迅速和可逆地控制，Shield-1 是一种可穿透细胞的药物。当从稳定转染的基因中表达时，抗原呈递的效率约为 2%，即每降解 50 个折叠的来源蛋白就会产生一个细胞表面 MHC I-肽复合物。相比之下，当相同的蛋白由痘苗病毒表达时，其抗原呈递效率降低约 10 倍，达到与其他痘苗病毒编码的模型抗原相似的水平。病毒感染本身并不会改变抗原加工的效率。相反，细胞内和病毒编码抗原之间的效率差异基于抗原是从转基因 mRNA 还是病毒编码的 mRNA 合成的。因此，I 类抗原加工机制可以根据其合成的精确细节区分折叠蛋白，从而调节抗原呈递效率。
