Promiscuous T cell epitope prediction of Candida albicans secretory aspartyl protienase family of proteins.
Candida albicans is one of the most important opportunistic dimorphic fungi responsible for hospital acquired fungal infection in humans. Candida infection rarely occurs in healthy individuals but it is frequently associated with patients who suffer from acquired immunodeficiency syndromes. To date, there is no effective vaccine against this fungal infection. Herein we demonstrated the use of immunomics to characterize promiscuous T cell epitope of C. albicans virulence factors by utilizing CandiVF, a C. albicans database previously constructed to be equipped with protein sequence analysis tool, three dimensional structure visualization software, sequence variable analysis program and Hotspot Hunter epitope prediction tool. Secretory aspartyl proteinase (Sap) family was chosen as a model to validate the Hotspot Hunter prediction. Analysis of Saps1-10 protein entries from CandiVF database revealed that a consensus T cell epitope was located at the C-terminal region of Saps1-10. The result of the in silico prediction was subsequently validated by conventional immunological methods. By using overlapping peptides span the predicted consensus T cell epitopes of Saps1-10 as stimulators, it was demonstrated that peptides S6 and S7 could stimulate PBMC proliferation in 9 of 12 blood donors. Interestingly, S2, the predicted T cell epitope of Sap2, was able to induce proliferation of all donors' PBMC. ELISpot assay for the detection of gamma-interferon producing clones confirmed that the peptide S2 actually stimulated T cell proliferation. The results suggest that S2 might be a potential candidate for vaccine development against C. albicans infection or to be utilized as an adjuvant to stimulate the pre-existing CD4+ T cell in other vaccine development.
Tongchusak
Songsak
S
Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
Brusic
Vladimir
V
Chaiyaroj
Sansanee C
SC
D000328:Adult; D000595:Amino Acid Sequence; D000946:Antigens, Fungal / Q000276:immunology; D016282:Aspartic Acid Endopeptidases / Q000276:immunology* / Q000378:metabolism; D002176:Candida albicans / Q000201:enzymology* / Q000276:immunology*; D049109:Cell Proliferation; D016384:Consensus Sequence; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D022142:Secretory Vesicles / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D000946:Antigens, Fungal; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016282:Aspartic Acid Endopeptidases