Faculty Collaboration Database

Generation of Th1 T cell responses directed to a HLA Class II restricted epitope from the Aspergillus f16 allergen. Clin Exp Immunol 2005 Feb;139(2):257-67

Date

01/19/2005

Pubmed ID

15654824

Pubmed Central ID

PMC1809287

DOI

10.1111/j.1365-2249.2005.02699.x

Scopus ID

2-s2.0-13544269242 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

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.

Author List

Ramadan G, Davies B, Kurup VP, Keever-Taylor CA

MESH terms used to index this publication - Major topics in bold

Allergens
Antigens, CD
Antigens, Plant
Aspergillosis
Aspergillus fumigatus
Cell Line
Cell Proliferation
Dendritic Cells
Desensitization, Immunologic
Epitopes
Fungal Proteins
HLA-DR Antigens
HLA-DRB1 Chains
Humans
Lymphocyte Activation
Lysosomal-Associated Membrane Protein 1
Microbiological Techniques
Th1 Cells