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Penetratin tandemly linked to a CTL peptide induces anti‐tumour T‐cell responses via a cross‐presentation pathway
Author(s) -
Pouniotis Dodie S.,
Apostolopoulos Vasso,
Pietersz Geoffrey A.
Publication year - 2006
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02304.x
Subject(s) - cytotoxic t cell , biology , antigen presentation , microbiology and biotechnology , mhc class i , major histocompatibility complex , pinocytosis , epitope , antigen presenting cell , cd8 , antigen , receptor , endocytosis , biochemistry , in vitro , immunology
Summary 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.