In silico prediction and immunological validation of common HLA-DRB1-restricted T cell epitopes of Candida albicans secretory aspartyl proteinase 2

Songsak Tongchusak, Chanvit Leelayuwat, Vladimir Brusic, Sansanee C. Chaiyaroj

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Sap2 is the most abundant virulence factor expressed during Candida infection, and the principal protein known to induce antibody response during Candida infection in humans. Its role in T-cell activation however, has not yet been determined. Sequence analysis revealed that Sap2 contains two variable regions:Var1 and Var2.Computational predictions by the Hotspot Hunter program identified that Var1 contains three candidate T-cell epitopes, whereas Var2 contains four. Thirty-nine overlapping peptides of Sap2 were then synthesized, and tested for their ability to induce proliferation of PBMC from 12 donors. Peptides P11, P17 and P31 exhibited significantly higher proliferative indices when compared with those of other peptides or controls. P17 and P31 are located in the areas of prediction, while P11 is not. There were other peptides outside the prediction areas that could stimulate PBMC proliferation at low levels. Nevertheless, the proliferative noise caused by such peptides was ruled out by IL-2 ELISpot analysis. Only P17 and P31 were shown to induce clonal proliferation of IFN-γ producing lymphocytes, suggesting that these two peptides contain T cell epitopes. P11, which stimulated IL-2 producing clones, contains a known B-cell epitope. Interestingly, P17 and P31 elicited both Th1 and Th2 cell responses with significant numbers of IL-13 secreting clones in response to stimulation. Taken together, the computer-based T cell epitope prediction method could identify the immunogenic T cell epitopes of C. albicans Sap2 that promiscuously bind to the HLA-DRB1 supertype.

Original languageEnglish
Pages (from-to)231-242
Number of pages12
JournalMicrobiology and Immunology
Volume52
Issue number4
DOIs
Publication statusPublished - Apr 2008

Keywords

  • C. Albicans
  • HLA-DRB1 restriction
  • Secretory aspartyl proteinase
  • T cell epitope prediction

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Virology

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