A novel Th cell epitope of Candida albicans mediates protection from fungal infection.

Details

Serval ID
serval:BIB_6B17E7D725E8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A novel Th cell epitope of Candida albicans mediates protection from fungal infection.
Journal
Journal of Immunology
Author(s)
Bär E., Gladiator A., Bastidas S., Roschitzki B., Acha-Orbea H., Oxenius A., LeibundGut-Landmann S.
ISSN
1550-6606 (Electronic)
ISSN-L
0022-1767
Publication state
Published
Issued date
2012
Volume
188
Number
11
Pages
5636-5643
Language
english
Abstract
Fungal pathogens are a frequent cause of opportunistic infections. They live as commensals in healthy individuals but can cause disease when the immune status of the host is altered. T lymphocytes play a critical role in pathogen control. However, specific Ags determining the activation and function of antifungal T cells remain largely unknown. By using an immunoproteomic approach, we have identified for the first time, to our knowledge, a natural T cell epitope from Candida albicans. Isolation and sequencing of MHC class II-bound ligands from infected dendritic cells revealed a peptide that was recognized by a major population of all Candida-specific Th cells isolated from infected mice. Importantly, human Th cells also responded to stimulation with the peptide in an HLA-dependent manner but without restriction to any particular HLA class II allele. Immunization of mice with the peptide resulted in a population of epitope-specific Th cells that reacted not only with C. albicans but also with other clinically highly relevant species of Candida including the distantly related Candida glabrata. The extent of the reaction to different Candida species correlated with their degree of phylogenetic relationship to C. albicans. Finally, we show that the newly identified peptide acts as an efficient vaccine when used in combination with an adjuvant inducing IL-17A secretion from peptide-specific T cells. Immunized mice were protected from fatal candidiasis. Together, these results uncover a new immune determinant of the host response against Candida ssp. that could be exploited for the development of antifungal vaccines and immunotherapies.
Keywords
Animals, Candida albicans/immunology, Candidiasis/immunology, Candidiasis/prevention & control, Cell Line, Epitopes, T-Lymphocyte/immunology, Fungal Vaccines/administration & dosage, Fungal Vaccines/immunology, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Helper-Inducer/immunology, T-Lymphocytes, Helper-Inducer/microbiology, Vaccines, Subunit/administration & dosage, Vaccines, Subunit/immunology
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2012 18:17
Last modification date
20/08/2019 15:25
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