A 16-mer peptide (RQIKIWFQNRRMKWKK) from antennapedia preferentially targets the Class I pathway.
Translocation of antigenic peptides into the cytosol of antigen presenting cells facilitates proteosomal processing and loading into Class I molecules for MHC presentation on the cell surface. The DNA binding domain of the Drosophila transcription factor (Antennapedia), a 60 amino acid protein, is rapidly taken up by cells and has been fused to selected antigens to enhance their immunogenicity. We now demonstrate that a 16 amino acid peptide from antennapedia can facilitate the cytoplasmic uptake of CTL epitope 9-mer peptides. Synthetic peptides were made containing the 16-mer antennapedia peptide linked in tandem to the ovalbumin SIINFEKL CTL peptide. The peptide complex was shown to rapidly internalise into APCs by confocal microscopy. This peptide induced CTL in C57BL/6 mice and protected them against growth of an ovalbumin expressing tumour cell line (E.G7-OVA). The ability of the hybrid peptide to be processed and presented by APCs was similar, whether the SIINFEKL sequence was appended at the C-terminus or N-terminus of the Antennapedia peptide. The production of synthetic peptides containing other CTL peptide epitopes may be useful for priming CTLs in vitro and in vivo
Pietersz
G A
GA
The Austin Research Institute, Studley Road, Heidelberg, 3084, Victoria, Australia. g.pietersz@ari.unimelb.edu.au
Li
W
W
Apostolopoulos
V
V
D000595:Amino Acid Sequence; D000818:Animals; D051943:Antennapedia Homeodomain Protein; D017951:Antigen Presentation; D001693:Biological Transport, Active; D003593:Cytoplasm / Q000276:immunology; D004330:Drosophila / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D029721:Drosophila Proteins; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006822:Hybrid Cells; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010047:Ovalbumin / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014407:Tumor Cells, Cultured
D051943:Antennapedia Homeodomain Protein; C497974:Antp protein, Drosophila; D029721:Drosophila Proteins; D015395:Histocompatibility Antigens Class I; D018398:Homeodomain Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D010047:Ovalbumin