TAP-Independent presentation of CTL epitopes by trojan antigens
TAP-Independent presentation of CTL epitopes by trojan antigens
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DOI：
10.4049/jimmunol.166.12.7063
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发表时间：
2001-06-15
影响因子：
4.4
通讯作者：
Celis, E
中科院分区：
文献类型：
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作者：
Lu, J;Wettstein, PJ;Celis, E
大多数CTL表位来源于细胞内蛋白，其在细胞质中被蛋白酶体降解成肽，所述肽被TAP复合物转运到内质网中。这些肽可以进一步加工成最佳大小（8-10个残基），用于与新生的MHC I类分子结合，产生输出到细胞表面的复合物。含有CTL表位的蛋白质或肽可以通过将它们连接到膜易位特洛伊载体而引入APC的细胞质中，从而允许它们掺入MHC I类Ag加工途径中。目前的研究结果表明，这些“特洛伊”抗原可以被运输到内质网中的TAP-独立的方式，在那里他们被加工和修剪成CTL表位。此外，在内肽酶弗林蛋白酶的参与下，也可能在羧肽酶的额外参与下，特洛伊抗原的加工也可以发生在高尔基体的反式隔室中。我们相信这些发现将对设计用于治疗或预防传染病和恶性疾病的CTL诱导疫苗具有价值。
The majority of CTL epitopes are derived from intracellular proteins that are degraded in the cytoplasm by proteasomes into peptides that are transported into the endoplasmic reticulum by the TAP complex. These peptides can be further processed into the optimal size (8-10 residues) for binding with nascent MHC class I molecules, generating complexes that are exported to the cell surface. Proteins or peptides containing CTL epitopes can be introduced into the cytoplasm of APCs by linking them to membrane-translocating Trojan carriers allowing their incorporation into the MHC class I Ag-processing pathway. The present findings suggest that these "Trojan" Ags can be transported into the endoplasmic reticulum in a TAP-independent way where they are processed and trimmed into CTL epitopes. Furthermore, processing of Trojan Ags can also occur in the trans-Golgi compartment, with the participation of the endopeptidase furin and possibly with the additional participation of a carboxypeptidase. We believe that these findings will be of value for the design of CTL-inducing vaccines for the treatment or prevention of infectious and malignant diseases.