Department of Biochemistry, Molecular Biology III and Inmunology, Faculty of Medicine, University of Granada, Parque Tecnológico de la Salud, Avd. de la Investigación nº 11, Tower C. 11th floor, Granada, 18071, Spain.
Centre for Genomics and Oncological Research: Pfizer, Andalusian Regional Government, GENYO, University of Granada, Parque Tecnológico de la Salud, Granada, Spain.
Hum Genomics. 2024 Sep 4;18(1):94. doi: 10.1186/s40246-024-00654-0.
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.
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.
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.
Present results suggest that severe patients younger than 55 may have a compromised TCR repertoire contributing to a worse disease outcome.
T 细胞群体的结构和动态对于协调对 SARS-CoV-2 的免疫反应至关重要。在我们的研究中，我们使用 T 细胞受体测序（TCRseq）来研究 173 名感染后 COVID-19 患者的 TCR 谱。
该队列包括 98 例轻症和 75 例重症病例，中位年龄为 53 岁。我们扩增并测序了 TCR β 链互补决定区 3（CDR3b），并进行了生物信息学分析，以评估年龄、性别和严重程度组之间的 repertoire 多样性、克隆性和 V/J 等位基因使用情况。通过聚类结构基序和过滤验证的反应性 CDR3b 对 COVID-19 进行 CDR3b 氨基酸序列推断。
我们的结果表明，55 岁以下的重症 COVID-19 患者的 TCR repertoire 多样性明显降低，克隆性扩张增加。这些结果反映了 55 岁以上患者的观察趋势（轻症和重症）。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与 55 岁以上的患者相似，同时伴有 COVID-19 相关基序的频率偏斜。
目前的结果表明，55 岁以下的重症患者可能存在受损的 TCR repertoire，导致疾病结局更差。
