Pathogen-derived peptide–Human Leukocyte Antigen complexes from influenza and respiratory viruses (pHLA complexes)

Pathogen-derived peptide–Human Leukocyte Antigen (pHLA) complexes are molecular structures formed by the association of intracellularly processed viral protein fragments with host HLA molecules. These complexes are transported to the cell surface, where they act as signals indicating the presence of an intracellular infection to the adaptive immune system (PubMed: 25108026). In respiratory infections like influenza or COVID-19, CD8+ cytotoxic T cells recognize specific pHLA complexes via their T-cell receptors (TCRs), leading to the destruction of the infected cell and the limitation of viral spread (PubMed: 32473127). Because these complexes are highly specific to the viral strain and the host's genetic HLA profile, they are central to the development of T-cell-inducing vaccines and advanced immunotherapies. Current therapeutic approaches include TCR-engineered T cells (TCR-T) and bispecific molecules that bridge the pHLA complex with T-cell activating receptors. However, the high diversity of HLA alleles in the human population and the potential for viruses to mutate their epitopes (antigenic drift) present significant hurdles for universal therapy design (Janeway's Immunobiology).

Other names

Peptide-MHC complexespMHCViral peptide-HLA complexesHLA-restricted viral antigensAntigen-presenting complexes

Recognition by T-cell receptors (TCRs) on CD8+ or CD4+ T cells, triggering cytokine release and programmed cell death of the infected host cell.