Penetratin tandemly linked to a CTL peptide induces anti-tumour T-cell responses via a cross-presentation pathway.
Recently there has been increasing evidence to suggest that membrane translocating peptides enter cells by a receptor-dependent pathway. There have been some studies on the mechanism of major histocompatibility complex (MHC) class I presentation of membrane translocating peptides incorporating cytotoxic T lymphocyte epitopes. However, these have been on different cell lines and only a limited number of inhibitors of the antigen presentation pathway were used. Herein, we demonstrate a comprehensive study utilizing a full spectrum of inhibitors to various pathways of MHC class I to elucidate the mechanism of the membrane translocating peptide, penetratin from Antennapedia (Int). It is clear that Int, RQIKIWFQNRRMKWKK when tandemly linked to a cytotoxic T lymphocyte peptide of ovalbumin, SIINFEKL (IntSIIN) is endocytosed via phagocytosis or macropinocytosis by dendritic cells in an ATP-dependent manner and is processed by a proteasome- and tapasin-independent pathway for presentation and loading to MHC class I molecules. In addition, the majority of antigen is taken up by negatively charged receptors. IntSIIN activates T cells in vitro and in vivo and protects mice against challenge with an ovalbumin-expressing tumour.
Immunology and Vaccine Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Victoria, Australia.
Dodie S
DS
Pouniotis
Vasso
V
Apostolopoulos
Geoffrey A
GA
Pietersz
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D057846:Cell-Penetrating Peptides; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D011992:Endosomes / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008247:Lysosomes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D007371:Interferon-gamma; C414409:penetratin