Viral peptide-Human Leukocyte Antigen complex (pHLA)

Viral peptide-Human Leukocyte Antigen (pHLA) complexes are essential molecular assemblies presented on the surface of virus-infected cells, serving as the primary recognition signal for the adaptive immune system (Murphy & Weaver, Janeway's Immunobiology, 2016). These complexes are formed when intracellular viral proteins are proteolytically processed into short peptides and loaded onto HLA Class I or Class II molecules within the endoplasmic reticulum or endocytic compartments (Robinson et al., Nucleic Acids Res, 2015). Once displayed on the cell surface, the pHLA complex is recognized by the T-cell receptor (TCR) of CD8+ or CD4+ T cells, triggering an immune response that leads to the destruction of the infected cell. In modern pharmacology, these complexes are exploited as highly specific therapeutic targets for TCR-engineered T cells (TCR-T) and bispecific T-cell engagers, such as Immune Mobilizing Monoclonal TCRs Against Virus (ImmTAVs) (Jakobsen et al., Nat Rev Drug Discov, 2022). These therapies aim to bypass natural immune exhaustion or evasion by providing high-affinity recognition of conserved viral epitopes, such as those from HIV, HBV, or HPV (Immunocore Pipeline, 2024). However, the extreme polymorphism of the HLA system requires patient-specific HLA matching, and the risk of cross-reactivity with similar self-peptides remains a critical safety consideration in drug development.

Other names

pMHCPeptide-MHC complexViral antigen-HLA complexMHC-restricted viral antigenViral pMHC

T-cell receptor (TCR) mediated recognition and redirection of cytotoxic T-cell activity against infected cells.