Analysis of TCR Repertoire by High-Throughput Sequencing Indicates the Feature of T Cell Immune Response after SARS-CoV-2 Infection

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.

T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer

“…Single-cell sequencing has been used to compare the TCR repertoire between COVID-19 patients and healthy controls, observing a very significant reduction in TCR clones diversity and disease-related changes in V and J gene usage, with less gene subfamilies and preferential V-J combinations used in COVID-19 patients. Those findings have been confirmed by others [ 137 , 138 ], specifying that the preferential V(D)J sequences only exist in the convalescent patients [ 137 ].…”

“…Some shared TCRs sequences appeared 2 weeks after convalescence and persisted up to 6 months, suggesting these clones might represent the T-memory phenotype associated with the disease [ 137 ]. The same observation has been reported in a population of antibody-seronegative convalescent individuals with asymptomatic and mild COVID-19, where the presence of SARS-CoV-2-specific polyfunctional stem-like memory phenotype T-cells in the peripheral blood suggests that an effective T-cell response may exert sufficient immune protection against the virus, even in the absence of neutralizing antibodies [ 127 , 139 ].…”

“…Another suggestion from Y. Wang and colleagues is that cross-reactive CD4+ and CD8+ T-cells lymphocytes contribute to SARS-CoV-2 infection resistance via the production of a virus-specific TCR recombination pattern [ 137 ] as overlap indices of TCRB CDR3 amino acid sequences are higher in COVID-19 patients. Those data are now helping to fingerprint a shared clonal expression responsible for the anti-SARS-CoV-2 immunity within a population of COVID-19 patients and of vaccinated individuals, which are protected by the most adverse events related to COVID-19.…”

Comparative multi-OMICS single cell atlas of five COVID-19 (rAdVV and mRNA) vaccines describe unique and distinct mechanisms of action

“…Furthermore, T cell receptor (TCR) genes such as TRAV8-4, TRAV26-2, TRBV28, TRBV30 and TRBV4-2 were also upregulated after rAdVV vaccination. TRAV8-4 genes found be expanded in COVID-19 convalescent 43 , thus it could be reflecting that rAdVV vaccination have spike specific NKT cell activation. In case of mRNA (PoV2/3) vaccines based upon upregulated genes, pathway analysis revealed that NKT cells should be positively regulating activation of other cell types including platelets activation and aggregation, cell adhesion, cellular defence response, chemokine signalling pathways, and infection of human immunodeficiency virus 1.…”

Post‐hospitalization rehabilitation alleviates long‐term immune repertoire alteration in COVID‐19 convalescent patients

“…Serologic analysis discovered that protective adaptive immune responses of anti-SARS-CoV-2 antibodies and specific memory B and T cell responses caused by natural SARS-CoV-2 infection may last for at least 6-8 months after the onset of symptoms, 28 and the diversity of the immune repertoire in convalescent patients with COVID-19 is associated with outcomes. 29 Although for most of the people infected with COVID-19, the symptoms are mild, even asymptomatic, 30,31 the long-term effect of COVID-19 infection on the immune system still attracts tremendous public attention. Here, we discovered characteristic pan-immune repertoire alterations, like lymphopenia, reduced unique CDR3 number and reduced diversity, together with the…”