The Aspergillus
allergen Asp f16 has been shown to confer protective Th1 T cell-mediated immunity against
infection with Aspergillus conidia in murine models. Here, we use overlapping (11-aa overlap with preceding
peptide) pentadecapeptides spanning the entire 427-aa coding region of Asp f16 presented on autologous dendritic cells (DC) to evaluate the ability of this
antigen to induce Th1 responses in humans. Proliferative responses were induced in five out of five donors, and one line with a high frequency of
interferon (IFN)-gamma-producing CD4(+) T cells in response to the complete
peptide pool was characterized. This line was cytotoxic to autologous pool-pulsed and Aspergillus culture extract-pulsed targets. Limitation of cytotoxicity to the CD4(+) T cell subset was demonstrated by co-expression of the degranulation marker CD107a in response to
peptide pool-pulsed targets. Cytotoxic T lymphocytes (CTL) killed Aspergillus hyphae and CTL culture supernatant killed Aspergillus conidia. By screening 21 smaller pools and individual
peptides shared by positive pools we identified a single candidate sequence of TWSIDGAVVRT that elicited responses equal to the complete pool. The defined
epitope was presented by human leucocyte
antigen (HLA)-DRB1-0301. These data identify the first known Aspergillus-specific
T cell epitope and support the use of Asp f16 in clinical
immunotherapy protocols to prime protective immune responses to prevent or treat
Aspergillus infection in immunocompromised patients.