对 CD8+ T 细胞表位识别的预测有多可靠?对癌症的启示

Onco Pub Date : 2024-04-17 DOI:10.3390/onco4020006
A. Lehmann, Paul V Lehmann, Stephen Todryk
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摘要

在 ELISPOT/ImmunoSpot® 等检测方法中,源自抗原序列的合成肽是检测 CD8+ 细胞毒性 T 淋巴细胞 (CTL) 的基本试剂。事实上,多肽与 ImmunoSpot® 的结合已被广泛用于众多疫苗试验中的免疫监测。病原体或癌症中的靶抗原可能体积大、数量多,因此往往需要使用针对某些 HLA 等位基因的算法和程序来进行肽表位预测,以缩小所需肽体的数量。在这篇评论中,我们结合对病毒和癌症抗原的免疫反应讨论了我们的数据,并得出结论:对 CD8+ T 细胞进行系统的高通量免疫监测,比依赖选定的 CD8+ T 细胞表位更能可靠地了解宿主对癌症的反应,无论这些表位是在硅学中预测的,还是根据经验确定的。我们展示了为实现这一目标进行大规模、高通量系统性 CD8+ T 细胞表位测试的可行性。
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How Reliable Are Predictions of CD8+ T Cell Epitope Recognition? Lessons for Cancer
Synthetic peptides derived from antigen sequences are essential reagents for the detection of CD8+ cytotoxic T lymphocytes (CTLs), in assays such as ELISPOT/ImmunoSpot®. Indeed, the combination of peptides and ImmunoSpot® has been widely used for immune monitoring in numerous vaccine trials. Target antigens in pathogens or cancers may be large in size and multiple in number, often seemingly necessitating in silico peptide epitope predictions using algorithms and programs for certain HLA alleles to narrow down the numbers of required peptides. In this commentary, we discuss our data in the context of immune responses to viral and cancer antigens, concluding that systematic high-throughput immune monitoring of CD8+ T cells will provide more reliable insights on the host’s response to cancer than the reliance on select CD8+ T cell epitopes, no matter whether these are in silico predicted or even if they had been empirically established. We show the feasibility of large scale, high-throughput systematic CD8+ T cell epitope testing towards this goal.
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