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. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. 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. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. 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. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations. Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.
【저자키워드】 SARS-CoV-2, viral infection, Immunological memory, ELISPOT, 【초록키워드】 immune response, Immunity, T cell assay, Infection, healthcare worker, Antigen, Protein, T cell, immune responses, response, T cell responses, understanding, immune function, antigens, ELISPOT, convalescent, characteristic, volunteers, T cell response, seronegative, pre-existing immunity, COVID-19 immune response, Protective, Lactate, cellular, identification, cross-reactive, proliferation, capture, Ex vivo, ORF3, subunit, PCR-confirmed, other coronaviruses, S1/S2, Cross-reactive immune responses, Memory responses, multiple antigens, T cell assays, uninfected, responses, populations, T cell proliferation, dependent on, Strong, cross-reactive immune response, ICS, infected with SARS-CoV-2, multiple antigen, 【제목키워드】 SARS-COV-2 infection, T cell assay, T cell, antiviral response, cross-reactive,