gms | German Medical Science

Vaccine strategies that target or activate dendritic cells in order to elicit potent cellular immunity are currently the subject of intense research. Here we report that genetically engineered yeast of the strain Saccharomyces cerevisiae expressing the full-length tumor associated antigen NY-ESO-1 are a versatile host for protein production. Feeding of dendritic cells with soluble NY-Eso-1 protein resulted in protein uptake, processing and MHC class I cross-presentation of NY-ESO-1-derived peptides. This process was analysed using previously established CD8+ T-cell clones and MHC-peptide specific antibodies recognizing the immuno-dominant NY-ESO-1157-165 peptide when presented by HLA-A2*0201 complexes. The process of antigen up-take and cross-presentation was dependent on the glycosylation pattern of NY-ESO-1 protein and the presence of accessible mannose receptors. Both, the production of NY-ESO-1 in protein O-mannosyltransferases deficient strains and blocking of mannose receptors on dendritic cells resulted in reduced levels of NY-ESO-1157-165 peptide presentation. In addition, NY-ESO-1 protein uptake by dendritic cells resulted in recognition by HLA-DP4 NY-Eso-1157-170 specific CD4+ T-cell lines indicating MHC class II presentation. Together, these data demonstrate that yeast derived full-length NY-ESO-1 protein is processed and presented adequately by MHC class I and II complexes and warrant clinical trials to determine the potential value of Saccharomyces cerevisiae as host for vaccine development.