CD8 T 细胞通过 T 细胞受体 (TCR) 识别感染细胞和癌细胞，TCR 与靶细胞上的肽-MHC 复合物结合。 TCR 和肽-MHC 之间相互作用的亲和力有助于 CD8 T 细胞的抗原敏感性或功能亲合力。为了响应肽-MHC 刺激，TCR-CD3 复合物和 CD8 辅助受体被下调。我们量化了用 CMV、EBV 和 HIV 肽刺激人类 CD8 T 细胞后跨越八个 MHC 限制的 CD3 和 CD8 下调，观察到 CD3 和 CD8 下调水平与功能亲合力之间存在很强的相关性，无论肽病毒来源如何。在靶向肿瘤相关抗原的 TCR 转导 T 细胞中，TCR 肽亲和力的变化足以改变 CD3 和 CD8 的下调。相关性分析和广义线性模型表明 CD3 下调与亲和力具有更强的相关性。使用流式细胞术简单测量 CD3 下调，可用于识别临床环境中的高亲和力 CD8 T 细胞。© 作者 2023。由牛津大学出版社代表英国免疫学会出版。

CD8 T cells recognize infected and cancerous cells via their T cell receptor (TCR), which binds peptide-MHC complexes on the target cell. The affinity of the interaction between the TCR and peptide-MHC contributes to the antigen sensitivity, or functional avidity, of the CD8 T cell. In response to peptide-MHC stimulation, the TCR-CD3 complex and CD8 co-receptor are downmodulated. We quantified CD3 and CD8 downmodulation following stimulation of human CD8 T cells with CMV, EBV, and HIV peptides spanning eight MHC restrictions, observing a strong correlation between the levels of CD3 and CD8 downmodulation and functional avidity, regardless of peptide viral origin. In TCR-transduced T cells targeting a tumor-associated antigen, changes in TCR-peptide affinity were sufficient to modify CD3 and CD8 downmodulation. Correlation analysis and generalized linear modelling indicated that CD3 downmodulation was the stronger correlate of avidity. CD3 downmodulation, simply measured using flow cytometry, can be used to identify high-avidity CD8 T cells in a clinical context.© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.