Institute for Immunology, University Medical Center Mainz, Langenbeckstr. 1, 55131 Mainz, Germany.
Med Microbiol Immunol. 2012 Nov;201(4):463-73. doi: 10.1007/s00430-012-0266-x. Epub 2012 Sep 14.
Activation of CD8(+) cytotoxic T cells is crucial for the adaptive immune response against viral infections and the control of malignant transformed cells. Together with activation of costimulatory molecules like CD3 and CD28, CD8(+) T cells need activation of their unique T cell receptor via recognition of foreign peptide epitopes in combination with major histocompatibility complexes class I on the cell surface of professional antigen-presenting cells. Presentation of pathogen-associated proteins is the result of a complex proteolytic process. It starts with the breakdown of proteins by a cytosolic endopeptidase, the proteasome, and is continued by subsequent N-terminal trimming events in the cytosol and/or the endoplasmic reticulum. Analysis of the proteolytic aminopeptidase activity in the former cellular compartment showed that the cytosol harbors a multitude of aminopeptidases that have singular specificities, but on the other hand also show redundancy in the trimming of N-terminal residues. The observed pattern of the overall trimming in the cytosol is reflected by the activity of the four identified aminopeptidases, and the administration of protease inhibitors made it possible to assign specificity of cleaving of proteinogenic amino acids to one or more identified aminopeptidase. The only exception was the cleavage of aspartic acid, which is performed by one yet unidentified enzyme.
CD8(+) 细胞毒性 T 细胞的激活对于针对病毒感染的适应性免疫反应和恶性转化细胞的控制至关重要。与 CD3 和 CD28 等共刺激分子的激活一起，CD8(+) T 细胞需要通过识别表面表达主要组织相容性复合体 I 的专业抗原呈递细胞上的外来肽表位来激活其独特的 T 细胞受体。病原体相关蛋白的呈递是一个复杂的蛋白水解过程的结果。它始于细胞质内的内肽酶蛋白酶体对蛋白质的分解，然后在细胞质和/或内质网中进行后续的 N 端修剪事件。对前细胞区室中蛋白水解氨肽酶活性的分析表明，细胞质中含有多种具有单一特异性的氨肽酶，但另一方面，在 N 端残基的修剪中也存在冗余。在细胞质中观察到的整体修剪模式反映在鉴定的四种氨肽酶的活性上，并且蛋白酶抑制剂的给药使得将蛋白氨基酸的切割特异性分配给一种或多种鉴定的氨肽酶成为可能。唯一的例外是天冬氨酸的切割，这是由一种尚未鉴定的酶完成的。
