Fan R, Tykodi S S, Braciale T J
Beirne B. Carter Center for Immunology Research, Department of Microbiology, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
J Immunol. 2000 Feb 15;164(4):1669-80. doi: 10.4049/jimmunol.164.4.1669.
The Ag receptors on CD8+ CTL recognize foreign antigenic peptides associated with cell surface MHC class I molecules. Peptides derived from self proteins are also normally presented by MHC class I molecules. Here we report that an H-2Kd-restricted murine CD8+ CTL clone directed to an influenza hemagglutinin epitope can recognize a peptide derived from the murine mitochondrial aconitase enzyme in association with H-2Kd molecules. Surprisingly, this self peptide is not normally displayed on the cell surface associated with the restricting MHC class I molecule. Several lines of evidence suggest that this self peptide, although requiring association with the Kd molecule for CTL recognition, is not associated with this or other MHC class I allele under physiologic conditions in intact cells. Rather, it is sequestered in the cytoplasm associated with a carrier protein and is released only upon cell disruption. These results suggest a means of restricting the entry of self peptide into the class I pathway. In addition, this finding raises the possibility that self peptides sequestered within the cell can, after release from damaged cells, interact with MHC class I molecules on bystander cells and trigger autoimmune injury by virus-specific CTLs during viral infection.
CD8⁺细胞毒性T淋巴细胞（CTL）上的抗原受体识别与细胞表面MHC I类分子相关的外来抗原肽。来自自身蛋白质的肽通常也由MHC I类分子呈递。在此我们报告，一个针对流感血凝素表位的H-2Kd限制性小鼠CD8⁺CTL克隆能够识别与H-2Kd分子相关的源自小鼠线粒体乌头酸酶的肽。令人惊讶的是，这种自身肽通常不会与限制性MHC I类分子一起呈现在细胞表面。多条证据表明，这种自身肽虽然需要与Kd分子结合才能被CTL识别，但在完整细胞的生理条件下，它并不与该或其他MHC I类等位基因结合。相反，它被隔离在与一种载体蛋白相关的细胞质中，只有在细胞破裂时才会释放。这些结果提示了一种限制自身肽进入I类途径的方式。此外，这一发现增加了一种可能性，即细胞内隔离的自身肽在从受损细胞释放后，可与旁观者细胞上的MHC I类分子相互作用，并在病毒感染期间由病毒特异性CTL引发自身免疫损伤。
