The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Nature Communications volume 12, Article number: 2055 ( 2021) Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team,.Oxford Immunology Network Covid-19 Response T Cell Consortium,.T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses
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