Antigenic Properties and Processing Requirements of 65-Kilodalton Mannoprotein, a Major Antigen Target of Anti-CandidaHuman T-Cell Response, as Disclosed by Specific Human T-Cell Clones

Abstract

T-cell-mediated immunity is known to play a central role in the host response to Candida albicans. T-cell clones are useful tools for the exact identification of fungal T-cell epitopes and the processing requirements of C. albicans antigens. We isolated human T-cell clones from an HLA-DRB1*1101 healthy donor by using an antigenic extract (MP-F2) of the fungus. Specific clones were T-cell receptor ␣/␤ and CD4 ؉ /CD8 ؊ and showed a T-helper type 1 cytokine profile (production of gamma interferon and not interleukin-4). The large majority of these clones recognized both the natural (highly glycosylated) and the recombinant (nonglycosylated) 65-kDa mannoprotein (MP65), an MP-F2 minor constituent that was confirmed to be an immunodominant antigen of the human T-cell response. Surprisingly, most of the clones recognized two synthetic peptides of different MP65 regions. However, the peptides shared the amino acid motif IXSXIXXL, which may be envisaged as a motif sequence representing the minimal epitope recognized by these clones. Three clones recognized natural and pronase-treated MP65 but did not detect nonglycosylated, recombinant MP65 or the peptides, suggesting a possible role for polysaccharides in T-cell recognition of C. albicans. Finally, lymphoblastoid B-cell lines were efficient antigen-presenting cells (APC) for recombinant MP65 and peptides but failed to present natural, glycosylated antigens, suggesting that nonprofessional APC might be defective in processing highly glycosylated yeast proteins. In conclusion, this study provides the first characterization of C. albicans-specific human T-cell clones and provides new clues for the definition of the cellular immune response against C. albicans.

A Novel Th Cell Epitope of Candida albicans Mediates Protection from Fungal Infection

“…In addition to the Als proteins, the 65-kDa mannoprotein MP65 from Candida also act as a Th cell Ag as previously reported (18,19) and confirmed in this study, although the latter only activates a minor proportion of Candida-specific T cells, and the precise range of amino acids binding to MHCII have not been determined in case of MP65. Nevertheless, the common feature of these two Candida-derived T cell Ags is their localization to the fungal cell wall.…”

“…3). In the same experiments, we also included a peptide pool of MP65, which was previously reported to act as a fungus-derived Ag (18,19), and an Aspergillus fumigatus-derived peptide (p41) that has been proposed to cross-stimulate Candida-specific T cells (15). Similar to pATG, MP65 induced IL-17A production from Candida-specific T cells after secondary infection, but the response was much lower than the one induced by pALS (Fig.…”

Dormant Mycobacterium tuberculosis Fails To Block Phagosome Maturation and Shows Unexpected Capacity To Stimulate Specific Human T Lymphocytes

“…PPD-and MP65-specific MHC class II-restricted human CD4 + T cell clones (TCC) were isolated from a Mycobacterium bovis bacillus Calmette-Guérin (BCG)-vaccinated subject as previously described (24,25).…”

Systematic identification in silico of covalently bound cell wall proteins and analysis of protein-polysaccharide linkages of the human pathogen Candida glabrata

“…adhesins of the Als-family and Hwp1p) (Hoyer et al, 1999;Hoyer, 2001;Sundstrom, 2002;Cheng et al, 2003). Also, other functions related to Candida virulence, such as adhesion to plastics, biofilm formation and antigenicity, can be attributed to CWPs (Gomez et al, 1996;Chaffin et al, 1998;Nisini et al, 2001;Li & Palecek, 2003;Garcia-Sanchez et al, 2004). Recently, a genome-wide in silico survey identified 66 and 104 putative GPI proteins in S. cerevisiae and C. albicans (De Groot et al, 2003), respectively.…”