Viral peptide-Human Leukocyte Antigen complex (pHLA) (pHLA)

Viral peptide-Human Leukocyte Antigen (pHLA) complexes are essential molecular assemblies that present fragments of viral proteins on the surface of infected or virally transformed cells for recognition by the immune system (Murphy & Weaver, Janeway's Immunobiology, 2016). These complexes are formed when intracellular viral proteins are degraded by the proteasome into short peptides, which are then loaded onto HLA Class I molecules in the endoplasmic reticulum and transported to the cell membrane (Waldman et al., Nat Rev Immunol, 2020). In the context of chronic infections (e.g., HBV, HIV) or virally-driven malignancies (e.g., HPV-associated cervical cancer, EBV-associated lymphomas), these pHLA complexes act as highly specific targets for therapeutic intervention (Stevanović et al., Science, 2017). Modern immunotherapies, such as T-cell receptor (TCR) engineered T-cells and TCR-like antibodies, are designed to bind these complexes with high affinity, bypassing the need for surface-expressed whole proteins (Luo et al., Front Immunol, 2022). This approach allows for the targeting of internal viral oncogenes like HPV E6/E7 or EBV LMP1, which are critical for maintaining the transformed state of the cell (Draper et al., Nat Rev Cancer, 2020). However, the efficacy of these therapies is often restricted by the patient's specific HLA haplotype and the potential for tumors to escape immune detection by downregulating HLA expression (Garrido et al., Curr Opin Immunol, 2016).

Other names

Peptide-MHC complexpMHCMHC-restricted viral antigenViral pMHCViral pHLA

T-cell receptor (TCR) mediated recognition and lysis, T-cell redirection, TCR-like antibody binding