MHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA
MHC class I antigen processing distinguishes endogenous antigens based on their translation from cellular vs. viral mRNA
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DOI：
10.1073/pnas.1112387109
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发表时间：
2012-05-01
影响因子：
11.1
通讯作者：
Yewdell, Jonathan W.
中科院分区：
文献类型：
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作者：
Dolan, Brian P.;Sharma, Aditi A.;Yewdell, Jonathan W.
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由细胞渗透药物Shield-1快速可逆地控制。当从稳定转染的基因表达时，抗原呈递的效率类似于2%，也就是说，在Shield-1撤回时，每50个折叠的源蛋白降解产生一个细胞表面MHC I类-肽复合物。相比之下，当相同的蛋白质由牛痘病毒表达时，其抗原呈递效率降低至与其它牛痘病毒编码的模型抗原所报道的相似的值的10倍。病毒感染本身不会改变抗原处理的效率。相反，细胞和病毒编码的抗原之间的效率差异是基于抗原是否由转基因与病毒编码的mRNA合成。因此，I类抗原加工机制可以基于折叠蛋白质合成的精确细节来区分折叠蛋白质，以调节抗原呈递效率。
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 similar to 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 similar to 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.