Aspergillus peptide–HLA complex (Aspergillus-pHLA)

Aspergillus peptide–HLA complexes are molecular assemblies presented on the surface of host cells, such as dendritic cells or infected pulmonary cells, following the internal processing of Aspergillus fungal proteins. These complexes consist of a short fungal peptide (typically 8–15 amino acids) bound within the groove of a Human Leukocyte Antigen (HLA) molecule, either Class I (for CD8+ T cells) or Class II (for CD4+ T cells). They are critical for the adaptive immune system's ability to identify and respond to Aspergillus fumigatus, the primary causative agent of invasive aspergillosis in immunocompromised patients. By serving as highly specific markers of infection, these complexes are being explored as therapeutic targets for precision immunotherapies. Current approaches include the adoptive transfer of Aspergillus-specific T cells and the engineering of TCR-like antibodies or TCR-T cells that can selectively recognize these complexes to induce fungal clearance while sparing healthy tissues. Specific immunodominant epitopes, such as those derived from the Asp f16, Crf1, and Catalase 1 proteins, have been identified as promising candidates for these HLA-restricted therapeutic strategies.

Other names

Aspergillus-specific peptide-MHC complexAspergillus-specific pMHCAspergillus-restricted T-cell epitopeFungal peptide-HLA complexAspergillus fumigatus peptide-HLA complex

Recognition of the fungal peptide-HLA complex by T-cell receptors (TCRs) or TCR-like antibodies, which triggers the activation of cytotoxic T lymphocytes (CTLs) or T-helper cells. This leads to the release of cytotoxic granules (perforin, granzyme B) and pro-inflammatory cytokines (IFN-gamma, TNF-alpha) that directly damage fungal hyphae and conidia or activate other immune cells to clear the infection.