背景:T细胞群的结构和动力学对于协调SARS-CoV-2的免疫应答至关重要。在我们的研究中,我们使用T细胞受体测序(TCRseq)调查了173例感染后COVID-19患者的TCR谱。
方法:该队列包括98例轻度和75例重度病例,中位年龄为53岁。我们扩增并测序了TCRβ链互补决定区3(CDR3b),并进行了生物信息学分析以评估库多样性,克隆,和年龄之间的V/J等位基因使用,性别和严重程度组。CDR3b氨基酸序列的推断是通过对结构基序进行聚类,并过滤验证了与COVID-19的反应性CDR3b。
结果:我们的结果显示,年龄小于55岁的严重COVID-19患者的TCR库多样性明显下降,克隆扩增增加。这些结果反映了55岁以上患者(轻度和重度)的观察趋势。此外,我们发现,与疾病严重程度相关的关键V等位基因(TRBV14,TRBV19,TRBV15和TRBV6-4)的使用显著减少.值得注意的是,55岁以下的重症患者的等位基因模式类似于55岁以上的患者,伴随着与COVID-19相关的基序的倾斜频率。
结论:目前的结果表明,年龄小于55岁的严重患者可能具有受损的TCR库,从而导致更差的疾病结局。
BACKGROUND: The architecture and dynamics of T cell populations are critical in orchestrating the immune response to SARS-CoV-2. In our study, we used T Cell Receptor sequencing (TCRseq) to investigate TCR repertoires in 173 post-infection COVID-19 patients.
METHODS: The cohort included 98 mild and 75 severe cases with a median age of 53. We amplified and sequenced the TCR β chain Complementary Determining Region 3 (CDR3b) and performed bioinformatic analyses to assess repertoire diversity, clonality, and V/J allelic usage between age, sex and severity groups. CDR3b amino acid sequence inference was performed by clustering structural motifs and filtering validated reactive CDR3b to COVID-19.
RESULTS: Our results revealed a pronounced decrease in diversity and an increase in clonal expansion in the TCR repertoires of severe COVID-19 patients younger than 55 years old. These results reflect the observed trends in patients older than 55 years old (both mild and severe). In addition, we identified a significant reduction in the usage of key V alleles (TRBV14, TRBV19, TRBV15 and TRBV6-4) associated with disease severity. Notably, severe patients under 55 years old had allelic patterns that resemble those over 55 years old, accompanied by a skewed frequency of COVID-19-related motifs.
CONCLUSIONS: Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.