Peptide–Major Histocompatibility Complex presenting SARS-CoV-2 epitopes (pMHC (SARS-CoV-2))

Peptide–Major Histocompatibility Complex (pMHC) complexes on the surface of SARS-CoV-2 infected cells are the primary targets for T-cell mediated immunity, consisting of viral peptide epitopes bound to Human Leukocyte Antigen (HLA) molecules (Shomuradova et al., 2020; PubMed: 33033174). These complexes, particularly MHC Class I, present intracellularly processed viral fragments from proteins such as Spike, Nucleocapsid, and Membrane to CD8+ cytotoxic T cells (Nguyen et al., 2021; PubMed: 34556559). In the context of therapeutic development, these pMHCs are targeted by TCR-engineered T cells (TCR-T) and TCR-mimetic antibodies, which offer a way to bypass traditional antibody-neutralization limits by targeting internal viral proteins (Huisman et al., 2022; PubMed: 35493490). A major challenge is the high polymorphism of HLA alleles, necessitating the development of therapies specific to common alleles like HLA-A*02:01. Furthermore, SARS-CoV-2 employs immune evasion strategies, such as the ORF8-mediated downregulation of MHC-I, which can reduce the density of these targets on the cell surface (Zhang et al., 2021; PubMed: 33991484). Safety considerations are paramount, as the potential for cross-reactivity with similar self-peptides (molecular mimicry) could lead to severe off-target autoimmune responses (Nguyen et al., 2021; PubMed: 34556559).

Other names

SARS-CoV-2 pMHCHLA-peptide complexes (SARS-CoV-2)MHC-I presenting SARS-CoV-2 epitopesSARS-CoV-2 epitope-HLA complexes

Recognition of viral peptide-HLA complexes by engineered T-cell receptors or antibodies, leading to targeted destruction of infected cells through granzyme/perforin release or antibody-mediated effector functions.