Cardiff University, School of Medicine, Heath Park, Cardiff, UK.
Cardiff University, School of Medicine, Heath Park, Cardiff, UK; Monash Biomedicine Discovery Institute, 19 Innovation Walk, Clayton, Victoria 3800, Australia.
Cell Rep. 2020 Jul 14;32(2):107885. doi: 10.1016/j.celrep.2020.107885.
T cell recognition of peptides presented by human leukocyte antigens (HLAs) is mediated by the highly variable T cell receptor (TCR). Despite this built-in TCR variability, individuals can mount immune responses against viral epitopes by using identical or highly related TCRs expressed on CD8 T cells. Characterization of these TCRs has extended our understanding of the molecular mechanisms that govern the recognition of peptide-HLA. However, few examples exist for CD4 T cells. Here, we investigate CD4 T cell responses to the internal proteins of the influenza A virus that correlate with protective immunity. We identify five internal epitopes that are commonly recognized by CD4 T cells in five HLA-DR1 subjects and show conservation across viral strains and zoonotic reservoirs. TCR repertoire analysis demonstrates several shared gene usage biases underpinned by complementary biochemical features evident in a structural comparison. These epitopes are attractive targets for vaccination and other T cell therapies.
T 细胞通过人类白细胞抗原 (HLA) 呈递的肽的识别是由高度可变的 T 细胞受体 (TCR) 介导的。尽管 TCR 存在这种内置的变异性，但个体可以通过在 CD8 T 细胞上表达相同或高度相关的 TCR 来对抗病毒表位产生免疫反应。这些 TCR 的特征描述扩展了我们对控制肽-HLA 识别的分子机制的理解。然而，针对 CD4 T 细胞的例子很少。在这里，我们研究了与保护性免疫相关的甲型流感病毒内部蛋白的 CD4 T 细胞反应。我们鉴定了五个在五个 HLA-DR1 个体中被 CD4 T 细胞共同识别的内部表位，并在病毒株和人畜共患病宿主中表现出保守性。TCR 库分析表明，在结构比较中明显存在互补生化特征的情况下，存在几个共享的基因使用偏倚。这些表位是疫苗接种和其他 T 细胞治疗的有吸引力的目标。
