The invention provides a polynucleotide comprising a sequence encoding a polypeptide that is capable of high level presentation of antigenic peptides on antigen-presenting cells, wherein the polypeptide comprises a β2-microglobulin molecule that is linked through its carboxyl terminal to a bridge peptide which spans the whole distance to the cell membrane, said bridge peptide being linked to a polypeptide stretch consisting of the full or partial transmembrane and/or cytoplasmic domains selected from the group consisting of a toll-like receptor (TLR) polypeptide, a CD40 polypeptide, and TLR and CD40 polypeptides fused in tandem, that allows the anchorage of the β2-microglobulin molecule to the cell membrane, and through its amino terminal to at least one antigenic peptide comprising an MHC class I epitope, wherein said antigenic peptide is preferably derived from a tumor-associated antigen or from a pathogenic antigen. Antigen presenting cells and DNA and cellular vaccines for treatment of cancer and infectious diseases, are also provided.