CD8 T Cell Epitope Distribution in Viruses Reveals Patterns of Protein Biosynthesis

Distinguishing T cell epitope distribution patterns is relevant for epitope-vaccine design. To that end, we invest0069gated the distribution of known CD8 T cell epitopes from Hepatitis C Virus, Human Immunodeficiency Virus-1 and Influenza A Virus using χ2 statistics. We found that epitopes are not distributed in the viral proteomes proportionally to the size of the source proteins. Specifically, capsid and matrix proteins pack significantly more epitopes than those expected by their size. Such non-homogeneous distribution cannot be accounted by underlying MHC I-peptide binding preferences nor it is related to sequence variability. Instead, we propose that it might be related to preferential protein translation/biosynthesis. Overall, these results support the prioritization of structural antigens for epitope identification and vaccine design.区分T细胞表位（T cell epitope）的分布模式，对于表位疫苗（epitope vaccine）的设计具有重要意义。为此，我们采用卡方检验（χ2 statistics），分析了丙型肝炎病毒（Hepatitis C Virus, HCV）、人类免疫缺陷病毒1型（Human Immunodeficiency Virus-1, HIV-1）以及甲型流感病毒（Influenza A Virus, IAV）的已知CD8⁺ T细胞表位（CD8 T cell epitopes）的分布特征。研究发现，表位在病毒蛋白质组（viral proteomes）中的分布并不与其来源蛋白的大小呈正比。具体而言，衣壳蛋白（capsid protein）与基质蛋白（matrix protein）所富集的表位数量，显著高于其蛋白大小所预期的水平。这种非均匀分布既无法通过潜在的MHC I类分子-肽结合偏好性（MHC I-peptide binding preferences）加以解释，也与序列变异性（sequence variability）无关。与之相反，我们推测该现象可能与偏好性蛋白质翻译/生物合成（protein translation/biosynthesis）过程相关。综上，本研究结果支持在表位鉴定与疫苗设计中优先选用结构性抗原（structural antigens）的策略。