Abstract
Coronavirus disease 2019 (COVID-19) is a global infectious disease caused by the SARS-CoV-2 coronavirus. T cells play an essential role in the body’s fighting against the virus invasion, and the T cell receptor (TCR) is crucial in T cell-mediated virus recognition and clearance. However, little has been known about the features of T cell response in convalescent COVID-19 patients. In this study, using 5′RACE technology and PacBio sequencing, we analyzed the TCR repertoire of COVID-19 patients after recovery for 2 weeks and 6 months compared with the healthy donors. The TCR clustering and CDR3 annotation were exploited to discover groups of patient-specific TCR clonotypes with potential SARS-CoV-2 antigen specificities. We first identified CD4+ and CD8+ T cell clones with certain clonal expansion after infection, and then observed the preferential recombination usage of V(D) J gene segments in CD4+ and CD8+ T cells of COVID-19 patients with different convalescent stages. More important, the TRBV6-5-TRBD2-TRBJ2-7 combination with high frequency was shared between CD4+ T and CD8+ T cells of different COVID-19 patients. Finally, we found the dominant characteristic motifs of the CDR3 sequence between recovered COVID-19 and healthy control. Our study provides novel insights on TCR in COVID-19 with different convalescent phases, contributing to our understanding of the immune response induced by SARS-CoV-2.
Highlights
Beginning in December 2019, the coronavirus disease 2019 (COVID-19) outbreak has posed a serious threat to more than 200 countries worldwide and has caused more than 5.2 million deaths
To evaluate the blood immune characteristics of COVID-19 patients with different convalescent stages, thirty-four samples were included in the current study, including nine COVID-19 patients with two-week convalescent stage, twenty COVID-19 patients at the six-month-convalescent stage, and five healthy controls (Table 1)
We found some unique VDJ recombination of TCR beta (TRB) was shared in both CD4+ T cells and CD8+ T cells of two-week convalescent COVID-19 patients, including TRBV6-5/D2/TRBJ2-7 and TRBV2/D1/TRBJ2-1, suggesting that these T cell clones with the above VDJ recombination were specific for SARS-CoV-2 antigen (Figure 3D,F)
Summary
Beginning in December 2019, the coronavirus disease 2019 (COVID-19) outbreak has posed a serious threat to more than 200 countries worldwide and has caused more than 5.2 million deaths (https://covid19.who.int. accessed on 13 December 2021). Beginning in December 2019, the coronavirus disease 2019 (COVID-19) outbreak has posed a serious threat to more than 200 countries worldwide and has caused more than 5.2 million deaths COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which usually leads to respiratory infections, and severe cases develop into severe pneumonia or even death [1,2,3]. The immune response to COVID-19 encompasses both B cell-mediated humoral responses through antibodies as well T cell activity. Many of the early studies on the immune response to SARS-CoV-2 have focused on neutralizing antibodies. A growing body of evidence suggests T cell responses are important for both early viral clearance as well as conferring protection through memory T cells for extended periods in COVID19 patients [4,5,6,7,8]. The specific T cell immune response against SARS-CoV-2, including the underlying mechanisms, remains unclear
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