SARS-CoV-2 ORF3a protein-derived peptides presented by major histocompatibility complex molecules (ORF3a-pMHC)

SARS-CoV-2 ORF3a protein-derived peptides presented by major histocompatibility complex (MHC) molecules are antigenic complexes essential for the cellular immune response against COVID-19 (UniProt P0DTC3). The ORF3a protein is a viral accessory protein that functions as a viroporin, modulating host cell processes such as autophagy and apoptosis, and activating the NLRP3 inflammasome (PubMed: 33065045). During infection, ORF3a is degraded into peptides that are presented on the cell surface by MHC Class I molecules, such as HLA-A*02:01, to be recognized by CD8+ T cells (PubMed: 34161331). These peptide-MHC (pMHC) complexes are primary targets for the development of T-cell receptor (TCR) engineered T-cell therapies and multi-epitope vaccines aimed at providing broad protection against SARS-CoV-2 (PubMed: 32835032). Targeting these complexes allows for the direct elimination of infected cells, potentially bypassing some of the limitations of antibody-based therapies that target the rapidly mutating Spike protein. However, the effectiveness of such therapies depends on the specific HLA alleles of the patient and the conservation of the ORF3a sequence across viral variants.

Other names

ORF3a peptide-MHC complexSARS-CoV-2 ORF3a T-cell epitopesORF3a-HLA complexSARS-CoV-2 ORF3a pMHCOpen reading frame 3a-derived antigens

T-cell receptor (TCR) binding to the peptide-MHC complex leading to T-cell activation and subsequent lysis of infected cells.