Reits Eric, Griekspoor Alexander, Neijssen Joost, Groothuis Tom, Jalink Kees, van Veelen Peter, Janssen Hans, Calafat Jero, Drijfhout Jan Wouter, Neefjes Jacques
Department of Tumor Biology and Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Immunity. 2003 Jan;18(1):97-108. doi: 10.1016/s1074-7613(02)00511-3.
Antigenic peptides generated by the proteasome have to survive a peptidase-containing environment for presentation by MHC class I molecules. We have visualized the fate and dynamics of intracellular peptides in living cells. We show that peptides are distributed over two different but interconnected compartments, the cytoplasm and the nucleus, and diffuse rapidly through and between these compartments. Since TAP is excluded from the nuclear face of the nuclear envelope, nuclear peptides have to leave the nucleus to contact TAP. Thereby, these peptides encounter cytosolic peptidases that degrade peptides within seconds unless bound to chromatin. Since peptide degradation is far more efficient than translocation, many peptides will be lost for antigen presentation by MHC class I molecules.
蛋白酶体产生的抗原肽必须在含有肽酶的环境中存活下来，以便由MHC I类分子进行呈递。我们已经观察到活细胞内肽的命运和动态。我们发现，肽分布在两个不同但相互连接的区室，即细胞质和细胞核中，并在这些区室之间快速扩散。由于转运体相关蛋白（TAP）被排除在核膜的核面之外，核内肽必须离开细胞核才能与TAP接触。因此，这些肽会遇到胞质肽酶，除非与染色质结合，否则这些肽酶会在几秒钟内降解肽。由于肽的降解比转运效率高得多，许多肽将无法用于MHC I类分子的抗原呈递。
