T-cell receptors specific for SARS-CoV-2 Membrane, Envelope, and Nucleocapsid-derived peptide–HLA complexes (SARS-CoV-2 M/E/N-specific TCRs)

T-cell receptors (TCRs) specific for SARS-CoV-2 Membrane (M), Envelope (E), and Nucleocapsid (N) proteins are specialized immune receptors that recognize viral peptides presented by Human Leukocyte Antigen (HLA) molecules on the surface of infected cells (Vasileiou et al., 2023). Unlike the Spike (S) protein, which is the primary target of most vaccines and monoclonal antibodies, the M, E, and N proteins are highly conserved across different SARS-CoV-2 variants, including Omicron and Delta (MDPI, 2024). These TCRs are the foundation for novel therapeutic approaches such as virus-specific T-cell (VST) therapy and TCR-engineered T-cell (TCR-T) therapy, which aim to provide cellular immunity to patients who cannot mount an effective response on their own (Immunity, 2020). By binding to these conserved epitopes, the TCRs trigger T-cell activation, leading to the direct lysis of infected cells and the release of antiviral cytokines like interferon-gamma (Frontiers in Immunology, 2021). This multi-antigen targeting strategy reduces the risk of viral immune escape and is currently being evaluated in clinical trials, such as those for the off-the-shelf product ALVR109, to treat severe COVID-19 in high-risk and immunocompromised populations (Vasileiou et al., 2023). These receptors are critical for long-term protection and are being studied for their ability to provide cross-reactive immunity against emerging variants (Nature Nanotechnology, 2022).

Other names

SARS-CoV-2 non-spike specific TCRsSARS-CoV-2 M/E/N-specific T-cell receptorsCOVID-19 VST TCRsSARS-CoV-2 structural protein-specific TCRs

Adoptive transfer of T cells expressing these TCRs enables the specific recognition of SARS-CoV-2 peptide-HLA complexes on infected cells, triggering T-cell activation, targeted cell lysis, and cytokine production.