A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation
A major role for TPPII in trimming proteasomal degradation products for MHC class I antigen presentation
复制标题
DOI：
10.1016/s1074-7613(04)00074-3
复制
发表时间：
2004-04-01
期刊：
影响因子：
32.4
通讯作者：
Neefjes, J
中科院分区：
文献类型：
--
作者：
Reits, E;Neijssen, J;Neefjes, J
细胞内蛋白质被蛋白酶体降解，并且所产生的存活于细胞质肽酶活性的肽可以由MHC I类分子呈递。在这里，我们表明，细胞内氨基肽酶降解肽在几秒钟内，几乎无关的氨基酸序列。N-而不是C-末端延伸增加了肽的半衰期，直到它们是15个氨基酸长。超过15个氨基酸，肽仅由肽酶TPPII修剪，其显示外肽酶和内肽酶活性。令人惊讶的是，大多数蛋白酶体降解产物在由MHC I类分子呈递之前由TPPII处理。我们定义了体内抗原加工过程中三种不同的蛋白水解活性。与抗原呈递相关的蛋白酶体产生的肽大多是15个氨基酸或更长。这些需要TPPII活性，以便在成为其他肽酶和MHC I类的底物之前进一步修整。氨肽酶的异质性池将TPPII产物加工成MHC I类肽及更高。
Intracellular proteins are degraded by the proteasome, and resulting peptides surviving cytoplasmic peptidase activity can be presented by MHC class I molecules. Here, we show that intracellular aminopeptidases degrade peptides within seconds, almost irrespectively of amino acid sequence. N- but not C-terminal extension increases the half-life of peptides until they are 15 amino acids long. Beyond 15 amino acids, peptides are exclusively trimmed by the peptidase TPPII, which displays both exo- and endopeptidase activity. Surprisingly, most proteasomal degradation products are handled by TPPII before presentation by MHC class I molecules. We define three distinct proteolytic activities during antigen processing in vivo. Proteasome-generated peptides relevant for antigen presentation are mostly 15 amino acids or longer. These require TPPII activity for further trimming before becoming substrates for other peptidases and MHC class I. The heterogeneous pool of aminopeptidases will process TPPII products into MHC class I peptides and beyond.