SARS-CoV-2 Spike protein peptide-Major Histocompatibility Complex (Spike-pMHC)

The SARS-CoV-2 Spike protein peptide-Major Histocompatibility Complex (Spike-pMHC) is a molecular assembly consisting of a short fragment of the viral Spike protein bound within the groove of a Major Histocompatibility Complex (MHC) molecule (Source: PMID: 33031767). These complexes are displayed on the surface of infected host cells and professional antigen-presenting cells (APCs) to signal the presence of the virus to the adaptive immune system (Source: PMID: 32843554). Recognition of these pMHCs by T-cell receptors (TCRs) on CD8+ and CD4+ T cells is the primary mechanism for the induction of cellular immunity and the destruction of infected cells (Source: NIH). In the context of COVID-19, specific epitopes like the HLA-A*02:01-restricted YLQPRTFLL peptide have been identified as dominant targets for cytotoxic T lymphocytes (Source: PMID: 33031767). Therapeutic strategies targeting these complexes include the development of TCR-engineered T-cell (TCR-T) therapies and TCR-like monoclonal antibodies, which aim to provide potent and specific elimination of infected cells (Source: PMID: 34620851). Additionally, COVID-19 vaccines function by inducing the expression of Spike proteins, which are subsequently processed into these pMHC complexes to prime the immune system (Source: PMID: 32843554). A significant challenge in targeting these complexes is the high degree of HLA polymorphism in the human population and the potential for viral mutations to cause immune escape by altering peptide binding or TCR recognition (Source: PMID: 33031767).

Other names

SARS-CoV-2 Spike pMHCSpike peptide-HLA complexS-peptide-MHCSpike-derived peptide-MHC complexSARS-CoV-2 Spike protein peptide-HLA complex

Therapeutic agents such as TCR-engineered T cells or TCR-mimetic antibodies bind specifically to the Spike-derived peptide presented within the MHC groove, leading to the activation of cytotoxic signaling and the subsequent lysis of the target cell (Source: PMID: 34620851).