Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences.
Major differences in transporter associated with antigen presentation (TAP)-dependent translocation of MHC class I-presentable peptides and the effect of flanking sequences.
复制标题
DOI：
10.4049/jimmunol.154.3.1273
复制
发表时间：
1995-02
影响因子：
4.4
通讯作者：
A. Neisig;J. Roelse;A. Sijts;F. Ossendorp;M. Feltkamp;W. Kast;C. Melief;Jacques Neefjes
中科院分区：
文献类型：
--
作者：
A. Neisig;J. Roelse;A. Sijts;F. Ossendorp;M. Feltkamp;W. Kast;C. Melief;Jacques Neefjes
MHC编码的与抗原提呈相关的转运蛋白(TAP)将多肽从胞浆转移到内质网管腔，在那里与MHC I类分子发生关联。MHC I类/肽复合体随后被转运到细胞表面，呈递给CD8+T细胞。我们通过竞争标记的模型肽的易位来研究定义的MHC I类可提示肽的TAP依赖的易位，以解决MHC I类分子高效的多肽递送是否先于TAP的等效多肽转位。令人惊讶的是，我们观察到被测试的16个多肽中的4个免疫优势病毒多肽被TAP非常低效地转运。低效率的转位可以通过取代多肽中第3位的Pro残基来克服。此外，在转运不良的多肽周围直接添加天然侧翼氨基酸可以显著改善TAP的易位。我们的数据表明，对于MHC I类结合，一些肽可以通过TAP有效地运输，而另一些肽则作为更大的肽片段运输，需要在内质网中进一步修剪才能与MHC I类结合。
The MHC-encoded transporter associated with Ag presentation (TAP) translocates peptides from the cytosol to the ER lumen, where association with MHC class I molecules occurs. The MHC class I/peptide complex is subsequently transported to the cell surface for presentation to CD8+T cells. We studied TAP-dependent translocation of defined MHC class I presentable murine peptides by competition for translocation of a radiolabeled model peptide, to address whether efficient peptide presentation by MHC class I molecules is preceded by equal efficient peptide translocation by TAP. Surprisingly, we observed that four immunodominant viral peptides of 16 peptides tested were very inefficiently transported by TAP. Inefficient translocation could be overcome by substitution of a proline residue present at position 3 in the peptides. Furthermore, addition of natural flanking amino acids directly surrounding a poorly transported peptide could considerably improve translocation by TAP. Our data suggest that some peptides are efficiently transported by TAP in their optimal size for MHC class I binding, whereas other peptides are transported as larger peptide fragments that need further trimming in the ER for MHC class I binding.