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- W4206913753 abstract "We generated CD4+ T cell lines (TCLs) reactive to either SARSCoV-2 spike (S) or membrane (M) proteins from unexposed naive T cells from six healthy donor volunteers to understand in fine detail whether the S and M structural proteins have intrinsic differences in driving antigen-specific CD4+ T cell responses. Having shown that each of the TCLs were antigen-specific and antigen-reactive, single cell mRNA analyses demonstrated that SARS-CoV-2 S and M proteins drive strikingly distinct molecular signatures. Whereas the S-specific responses are virtually indistinguishable from those responses induced by other viral antigens (e.g. CMV), the M protein-specific CD4+ TCLs have a transcriptomic signature that indicate a marked suppression of interferon signaling, characterized by a downregulation of the genes encoding ISG15, IFITM1, IFI6, MX1, STAT1, OAS1, IFI35, IFIT3 and IRF7 (a molecular signature which is not dissimilar to that found in severe COVID-19). Our study suggests a potential link between the antigen specificity of the SARS-CoV-2-reactive CD4+ T cells and the development of specific sets of adaptive immune responses. Moreover, the balance between T cells of significantly different specificities may be the key to understand how CD4+ T cell dysregulation can determine the clinical outcomes of COVID-19." @default.
- W4206913753 created "2022-01-26" @default.
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- W4206913753 date "2022-01-21" @default.
- W4206913753 modified "2023-09-23" @default.
- W4206913753 title "Antigenic determinants of SARS-CoV-2-specific CD4+ T cell lines reveals M protein-driven dysregulation of interferon signaling" @default.
- W4206913753 doi "https://doi.org/10.1101/2022.01.20.22269491" @default.
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