Abstract
COVID-19 disease outcome is highly dependent on adaptive immunity from T and B lymphocytes, which play a critical role in the control, clearance and long-term protection against SARS-CoV-2. To date, there is limited knowledge on the composition of the T and B cell immune receptor repertoires [T cell receptors (TCRs) and B cell receptors (BCRs)] and transcriptomes in convalescent COVID-19 patients of different age groups. Here, we utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. We discovered highly expanded T and B cells in multiple patients, with the most expanded clonotypes coming from the effector CD8+ T cell population. Highly expanded CD8+ and CD4+ T cell clones show elevated markers of cytotoxicity (CD8: PRF1, GZMH, GNLY; CD4: GZMA), whereas clonally expanded B cells show markers of transition into the plasma cell state and activation across patients. By comparing young and old convalescent COVID-19 patients (mean ages = 31 and 66.8 years, respectively), we found that clonally expanded B cells in young patients were predominantly of the IgA isotype and their BCRs had incurred higher levels of somatic hypermutation than elderly patients. In conclusion, our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.
Highlights
T and B lymphocytes are crucial for protection from SARS-CoV-2 infection, viral clearance and the formation of persisting antiviral immunity [1, 2]
In agreement with the overall higher expansion of CD8+ effector over CD4+ effector T cell subsets (Figures 2G, H), we found that the vast majority (85%) of the ten most expanded T cell receptors (TCRs) clonotypes per patient originated from CD8+ T cells (Supplemental Figure 5)
We investigated the patterns of clonal expansion in different T cell subsets by mapping single-cell TCR sequencing data onto individual CD8+ and CD4+ T cells visualized by UMAP (Figures 4A, B)
Summary
T and B lymphocytes are crucial for protection from SARS-CoV-2 infection, viral clearance and the formation of persisting antiviral immunity [1, 2]. Lymphocytes express either T cell receptors (TCR) or B cell receptors (BCR), which possess a highly diverse pair of variable chains [variable alpha (Va) and beta (Vb) for TCR and variable light (VL) and heavy (VH) for BCR] that are able to directly engage with antigen (e.g., viral proteins or peptides). Diversity in these variable chains are generated by somatic recombination of V-, D- and J-gene germline segments and along with combinatorial receptor chain pairing and somatic hypermutation (BCR only) results in an estimated human TCR and BCR diversity of 1018 and 1013, respectively [7, 8]. In the context of COVID-19, immune repertoire sequencing has shown diminished TCR repertoire diversity and BCR isotype switching and respective expansion during early disease onset [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
