IInstitut für Biochemie, Charité - Universitätsmedizin Berlin, 10117 Berlin, Germany; Berlin Institute of Health, 10117 Berlin, Germany; Centre for Inflammation Biology and Cancer Immunology (CIBCI) & Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, UK.
Max-Planck-Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
Trends Immunol. 2017 Dec;38(12):904-915. doi: 10.1016/j.it.2017.07.011. Epub 2017 Aug 19.
CD8 T cell specificity depends on the recognition of MHC class I-epitope complexes at the cell surface. These epitopes are mainly produced via degradation of proteins by the proteasome, generating fragments of the original sequence. However, it is now clear that proteasomes can produce a significant portion of epitopes by reshuffling the antigen sequence, thus expanding the potential antigenic repertoire. MHC class I-restricted spliced epitopes have been described in tumors and infections, suggesting an unpredicted relevance of these peculiar peptides. We review current knowledge about proteasome-catalyzed peptide splicing (PCPS), the emerging rules governing this process, and the potential implications for our understanding and therapeutic use of CD8 T cells, as well as mechanisms generating other non-canonical antigenic epitopes targeted by the T cell response.
CD8 T 细胞的特异性取决于细胞表面上 MHC Ⅰ类-表位复合物的识别。这些表位主要通过蛋白酶体降解蛋白质产生，生成原始序列的片段。然而，现在清楚的是，蛋白酶体可以通过重新排列抗原序列产生大量的表位，从而扩大潜在的抗原库。MHC Ⅰ类限制的剪接表位已在肿瘤和感染中被描述，这表明这些特殊肽具有意想不到的相关性。我们综述了关于蛋白酶体催化的肽剪接（PCPS）的现有知识，以及支配这一过程的新兴规则，以及对我们理解和治疗性应用 CD8 T 细胞的潜在影响，以及生成其他非经典抗原表位的机制，这些表位是 T 细胞反应的靶点。
