Hombach J, Pircher H, Tonegawa S, Zinkernagel R M
Department of Pathology, University of Zürich, Switzerland.
J Exp Med. 1995 Nov 1;182(5):1615-9. doi: 10.1084/jem.182.5.1615.
Peptides presented by major histocompatibility complex (MHC) class I molecules are derived from intracellularly synthesized proteins. Cytosolic proteins are fragmented into peptides, which are subsequently transported via the transporter of antigen presentation (TAP) into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. We have investigated the requirements for MHC class I presentation of the immunodominant gp33 cytotoxic T lymphocyte epitope of the lymphocytic choriomeningitis virus. This epitope is located within the leader peptide of the virus glycoprotein. Such an epitope is expected to be presented in a TAP-independent manner, since it is released into the ER by signal peptidase. Taking advantage of TAP1-/- mice, however, we show both in vitro and in vivo that, after virus infection, the presentation of the gp33 epitope is strictly dependent on a functional TAP heterodimer. The results are discussed with respect to peptide trimming processes in the ER.
主要组织相容性复合体（MHC）I类分子呈递的肽段来源于细胞内合成的蛋白质。胞质蛋白被切割成肽段，随后通过抗原呈递转运体（TAP）转运至内质网（ER），在那里它们与MHC I类分子结合。我们研究了淋巴细胞性脉络丛脑膜炎病毒免疫显性gp33细胞毒性T淋巴细胞表位的MHC I类呈递的要求。该表位位于病毒糖蛋白的前导肽内。由于该表位由信号肽酶释放到内质网中，预计它将以不依赖TAP的方式呈递。然而，利用TAP1-/-小鼠，我们在体外和体内均表明，病毒感染后，gp33表位的呈递严格依赖于功能性TAP异二聚体。针对内质网中的肽段修剪过程对结果进行了讨论。
