SARS-CoV-2 Spike protein peptide-MHC Class I complex (Spike-pMHC-I)

The SARS-CoV-2 Spike protein peptide-MHC Class I complex is a molecular assembly formed on the surface of infected or vaccinated cells, consisting of a proteolytically processed fragment of the viral Spike protein bound to a Major Histocompatibility Complex (MHC) Class I molecule. This complex serves as the essential ligand for the T-cell receptor (TCR) of CD8+ cytotoxic T cells, facilitating the recognition and subsequent destruction of cells harboring the virus (Grifoni et al., 2020, Cell). The interaction between the TCR and the Spike-pMHC-I complex is a cornerstone of the adaptive immune response, driving the clearance of SARS-CoV-2 and providing the basis for vaccine-induced protection (Saini et al., 2021, Science Immunology). In therapeutic development, this complex is targeted by TCR-engineered T-cell therapies and bispecific antibodies designed to enhance the immune system's ability to identify viral reservoirs. The stability of the complex and the specific peptide sequence presented are influenced by the host's HLA genotype, which determines the breadth and potency of the T-cell response (Shomuradova et al., 2020, Immunity). Monitoring these complexes is vital for assessing the impact of emerging viral variants on cellular immunity and for the design of next-generation immunotherapies.

Other names

SARS-CoV-2 Spike pMHC complexSpike-HLA-I complexSpike-peptide-MHC-IS-pMHCSpike-peptide-HLA complex

The complex presents viral epitopes to CD8+ T-cell receptors, initiating a signaling cascade that results in the release of cytotoxic molecules like perforin and granzyme to induce apoptosis in infected cells.