Viral peptide–Major Histocompatibility Complex (pMHC) (pMHC)

Viral peptide–Major Histocompatibility Complex (pMHC) molecules are essential cell-surface structures that present fragments of viral proteins to the immune system (Hewitt, 2003). These complexes are formed when viral antigens are processed into short peptides and loaded onto MHC Class I or II molecules within the host cell's endoplasmic reticulum. Once displayed on the cell surface, they serve as the primary target for T-cell receptors (TCRs) on CD8+ or CD4+ T-cells, initiating a targeted immune response against the infected cell (Durbas et al., 2020). In the context of chronic infections and viral-associated cancers, such as those caused by Epstein-Barr Virus (EBV) or Human Papillomavirus (HPV), these pMHCs are exploited as highly specific therapeutic targets. Drugs like Tabelecleucel and various TCR-engineered T-cell (TCR-T) therapies are designed to recognize these specific viral signatures to eliminate diseased cells while sparing healthy tissue (Prockop et al., 2020). However, the effectiveness of these therapies can be limited by viral mechanisms that downregulate MHC expression or by the risk of TCR cross-reactivity with similar self-peptides (EMA, 2022).

Other names

Viral pMHCPeptide-MHC complexpHLAMHC-restricted viral antigenViral peptide-HLA complex

Recognition by T-cell receptors (TCRs) or TCR-mimetic antibodies, leading to the formation of an immunological synapse and subsequent cytotoxic lysis of the infected cell via granzyme and perforin release.