RESUMEN
BACKGROUND: Antibodies induced by viral infection can not only prevent subsequent virus infection, but can also mediate pathological injury following infection. Therefore, understanding the B-cell receptor (BCR) repertoire of either specific neutralizing or pathological antibodies from patients convalescing from Coronavirus disease 2019 (COVID-19) infection is of benefit for the preparation of therapeutic or preventive antibodies, and may provide insight into the mechanisms of COVID-19 pathological injury. METHODS: In this study, we used a molecular approach of combining 5' Rapid Amplification of cDNA Ends (5'-RACE) with PacBio sequencing to analyze the BCR repertoire of all 5 IgH and 2 IgL genes in B-cells harvested from 35 convalescent patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: We observed numerous BCR clonotypes within most COVID-19 patients, but not in healthy controls, which validates the association of the disease with a prototypical immune response. In addition, many clonotypes were found to be frequently shared between different patients or different classes of antibodies. CONCLUSIONS: These convergent clonotypes provide a resource to identify potential therapeutic/prophylactic antibodies, or identify antibodies associated with pathological effects following infection with SARS-CoV-2.
Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Receptores de Antígenos de Linfocitos B/genética , Anticuerpos , Linfocitos BAsunto(s)
Anticuerpos Antivirales/sangre , Complejo Antígeno-Anticuerpo/sangre , Antígenos Virales/inmunología , COVID-19/diagnóstico , Glicoproteínas/inmunología , SARS-CoV-2/inmunología , Antígenos Virales/sangre , Antígenos Virales/genética , Biomarcadores/sangre , COVID-19/sangre , COVID-19/inmunología , COVID-19/virología , Estudios de Casos y Controles , Cromatografía de Afinidad , Glicoproteínas/sangre , Glicoproteínas/genética , Humanos , Sueros Inmunes/química , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Espectrometría de Masas en TándemRESUMEN
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.