Research On The Characteristics Of The Tcr Immune Repertoire In COVID-19 Patients

The outbreak of coronavirus disease 2019(COVID-19)has become a worldwide health threat since December 2019.However,the studies on the T cell receptor(TCR)bias in adaptive immunity induced by SARS-CoV-2 are relatively lacking.A comprehensive comparative analysis of TCR immune repertoire was performed to identify significant αβ TCR bias sequences caused by SARS-CoV-2 virus antigen including 94 moderate/mild or severe/critical symptomatic COVID-19 patients,as well as other 17 healthy controls.We used existing biology software including SPSS,Origin,Matlab and R software as the main graphing tools,and these data were derived from the comparison with cellranger vdj with-reference.The main research contents of this paper include:(1)Integrated analysis of COVID-19 scRNA-seq data: most of the patients were mildly and moderately symptomatic,and half of them were severely critical type or even died.We divided the patients into five groups: healthy control,moderately progressive,severely progressive,moderately convalescence,and severely convalescence to analyze the significant differences of the immune repertoire which included differences in TCR gene segment frequencies,differences in CDR3 and its corresponding segments,clone size,etc.(2)TCR preferences for moderate COVID-19 patients from progression to recovery stage;(3)Differences in the use of TCR segments between peripheral blood and bronchoalveolar lavage fluid: the incomplete knowledge of the host immune response to this life-threatening illness makes it difficult to find therapeutic agents and treatments that work.To determine the changes in variable(V),joining(J)and complementarity determining region of T cell receptor rearrangements in peripheral blood and bronchoalveolar lavage fluid after SARS-CoV-2infection.For these scTCR-seq data,samples of peripheral blood mononuclear cells(PBMCs)were grouped together and samples of bronchoalveolar lavage fluid were grouped together,with the aim of studying differential changes in immune cells in BALF and PBMC and early diagnosis of the disease.We observed that the most frequently used specific chains for moderate and severe patients were TRAV13-2-J45-TRBV5-4-J2-2 and TRAV19-J8-TRBV27-J2-5,respectively.Furthermore,considering that tracking the dynamics of immunome pool changes in COVID-19 patients may be a crucial suggestive biomarker for determining how the disease will develop and how it will respond to treatment,the significant differences were found in the 18 VJ pairs after 4 to 17 days apart,that is,when the patients entered the recovery period.Besides,the TCR bias of V and J gene segments were observed in peripheral blood mononuclear peripheral blood mononuclear cells(PBMCs)and bronchoalveolar lavage fluid(BALF).Our study provides overall analysis of the phase change characteristics of the TCR immune repertoire in COVID-19 patients,which contributes to the understanding of change of TCR induced by SARS-CoV-2.