T-cell receptor specific for MHC-presented SARS-CoV-2 nucleocapsid epitopes (TCR-SARS-CoV-2-N)

T-cell receptors (TCRs) specific for MHC-presented SARS-CoV-2 nucleocapsid (N) epitopes represent a class of therapeutic targets for adoptive cell therapy, particularly TCR-engineered T-cells (TCR-T). The nucleocapsid protein is a highly abundant and conserved structural protein of SARS-CoV-2, making it a more stable target than the rapidly mutating spike protein (Grifoni et al., 2020, Cell). These TCRs are designed to recognize specific viral peptides, such as the N105-113 (SPRWYFYYL) epitope, when presented by prevalent human leukocyte antigen (HLA) alleles like HLA-A*02:01 (Nguyen et al., 2021, Immunity). Upon recognition of the peptide-MHC complex on infected cells, the TCR triggers a robust cytotoxic response, including the release of granzymes and perforin, effectively clearing the viral reservoir (Le Bert et al., 2020, Nature). This approach is especially promising for immunocompromised patients who fail to generate adequate antibody responses or for treating severe COVID-19 cases where endogenous T-cell responses are exhausted. Current research focuses on identifying high-affinity TCR sequences and ensuring safety by minimizing cross-reactivity with the human proteome (Lineburg et al., 2021, Immunity). As a therapeutic modality, TCR-T cells targeting the nucleocapsid offer the potential for long-term, variant-proof immunity (Panagioti et al., 2022, Frontiers in Immunology).

Other names

SARS-CoV-2 nucleocapsid-specific T-cell receptorN-specific TCRSARS-CoV-2 N-reactive TCRHLA-A*02:01-restricted SARS-CoV-2 nucleocapsid TCR

Engineered T-cells expressing these TCRs recognize specific SARS-CoV-2 nucleocapsid peptides presented by Major Histocompatibility Complex (MHC) molecules on the surface of infected cells (Le Bert et al., 2020, Nature). Upon binding, the TCR triggers T-cell activation, leading to the release of cytotoxic granules such as perforin and granzymes, as well as proinflammatory cytokines like IFN-gamma, which results in the destruction of the infected cell (Nguyen et al., 2021, Immunity).