Understanding T cell responses to COVID-19 is essential for informing public health strategies

Abstract

Durable T cell responses to SARS-CoV-2 antigens after infection or vaccination improve immune-mediated viral clearance. To date, population-based surveys of COVID-19 adaptive immunity have focused on testing for IgG antibodies that bind spike protein and/or neutralize the virus. Deployment of existing methods for measuring T cell immunity could provide a more complete profile of immune status, informing public health policies and interventions.

Fig. 1.. Schematic of molecular and cellular technologies for the evaluation of T cell responses to SARS-CoV-2.

Molecular assay workflow (left) as shown is modeled on Adaptive Biotechnologies’ immunoSEQ platform (38). Genomic DNA and a control synthetic immune repertoire template (not shown in the illustration) are PCR-amplified in parallel using primers specific for V-J sequences and subsequently for introduction of sequencing adapters and barcodes. NGS is performed, and the generated sequences are fed to the binary classifier to obtain the final results. In the classifier and threshold call graph, the enhanced sequences count (y axis) refers to the number of identified public SARS-CoV-2–associated TCRs versus the total number of unique rearrangements (x axis) within a given sample. The diagnostic model threshold is set to a high predetermined specificity against a set of holdout negative controls not used in training. Cellular assays (right) require viable PBMCs and can use either ex vivo stimulation for functional readouts, as in ELISpots and ICS/AIM assays, versus direct labeling with HLA- and peptide-specific tetramers. ICS/AIM and tetramer-based approaches involve acquisition of samples by a flow cytometer.