记忆性CD8 T细胞在保护免受严重急性呼吸综合症冠状病毒2（SARS-CoV-2）突破感染方面发挥着重要作用。抗原暴露途径对这些细胞的功能影响是否显著不太明确。本研究比较了接种、感染或两者都经历后，对普遍SARS-CoV-2表位的记忆性CD8 T细胞反应。CD8 T细胞在直接体外重新刺激时展现出相当的功能能力，而不受抗原历史的影响。然而，T细胞受体使用的分析表明，接种与感染或两者结合相比，接种导致的范围更窄。重要的是，在体内召回模型中，来自感染个体的记忆性CD8 T细胞虽然增殖相等，但分泌的肿瘤坏死因子（TNF）较来自接种人群的较少。当感染个体也接种疫苗时，这种差异被抵消了。我们的发现阐明了在不同SARS-CoV-2抗原暴露途径后再感染易感性的差异。版权所有©2023作者。由Elsevier Inc.出版，保留所有权利。

Memory CD8 T cells play an important role in the protection against breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether the route of antigen exposure impacts these cells at a functional level is incompletely characterized. Here, we compare the memory CD8 T cell response against a common SARS-CoV-2 epitope after vaccination, infection, or both. CD8 T cells demonstrate comparable functional capacity when restimulated directly ex vivo, independent of the antigenic history. However, analysis of T cell receptor usage shows that vaccination results in a narrower scope than infection alone or in combination with vaccination. Importantly, in an in vivo recall model, memory CD8 T cells from infected individuals show equal proliferation but secrete less tumor necrosis factor (TNF) compared with those from vaccinated people. This difference is negated when infected individuals have also been vaccinated. Our findings shed more light on the differences in susceptibility to re-infection after different routes of SARS-CoV-2 antigen exposure.Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.