The source proteins from which CD8⁺ T cell-activating peptides are derived remain enigmatic. Glycoproteins are particularly challenging in this regard owing to several potential trafficking routes within the cell. By engineering a glycoprotein-derived epitope to contain an N-linked glycosylation site, we determined that optimal CD8⁺ T cell expansion and function were induced by the peptides that are rapidly produced from the exceedingly minor fraction of protein mislocalized to the cytosol. In contrast, peptides derived from the much larger fraction that undergoes translocation and quality control are produced with delayed kinetics and induce suboptimal CD8⁺ T cell responses. This dual system of peptide generation enhances CD8⁺ T cell participation in diversifying both antigenicity and the kinetics of peptide display.

衍生CD8 ⁺ T细胞活化肽的来源蛋白仍然是谜。由于细胞内几种潜在的运输途径，糖蛋白在这方面特别具有挑战性。通过工程化糖蛋白衍生的表位，使其包含一个N-连接的糖基化位点，我们确定了最佳的CD8 ⁺ T细胞扩增和功能是由从错误定位到胞质溶胶的极小部分蛋白快速产生的肽诱导的。相反，衍生自经历了易位和质量控制的更大片段的肽具有延迟的动力学，并诱导了次优的CD8 ⁺ T细胞反应。肽生成的双重系统增强了CD8 ⁺ T细胞参与使抗原性和肽展示动力学多样化。