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Whole protein and defined CD8 + and CD4 + peptides linked to penetratin targets both MHC class I and II antigen presentation pathways
Author(s) -
Pouniotis Dodie S,
Esparon Sandra,
Apostolopoulos Vasso,
Pietersz Geoffrey A
Publication year - 2011
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2011.13
Subject(s) - cytotoxic t cell , epitope , antigen , cd8 , biology , antigen presentation , antigen presenting cell , t cell , tumor antigen , mhc class i , antigen processing , microbiology and biotechnology , immune system , immunology , in vitro , biochemistry
Cytoplasmic delivery and cross‐presentation of proteins and peptides is necessary for processing and presentation of antigens for the generation of cytotoxic T cells. We previously described the use of the 16 amino acid peptide penetratin from the Drosophila Antennapedia homeodomain (penetratin, Antp) to transport cytotoxic T lymphocyte epitopes derived from ovalbumin (OVA) or the Mucin‐1 tumor‐associated antigen into cells. We have now shown that penetratin covalently conjugated to OVA protein and linked in tandem to CD4 + and/or CD8 + T‐cell epitopes from OVA‐stimulated T cells in vitro (B3Z T‐cell hybridoma and OT‐I and OT‐II T cells). The induction of these responses was directly mediated by the penetratin peptide as linking a nonspecific 16‐mer peptide to OVA or mixing did not induce CD8 + or CD4 + T‐cell responses in vitro . Furthermore, interferon (IFN)‐γ‐secreting CD4 + and CD8 + T cells were induced which suppressed B16.OVA tumor growth in C57BL/6 mice. Tumor protection was mediated by a CD8 + T‐cell‐dependent mechanism and did not require CD4 + help to protect mice 7 days after a boost immunization. Alternatively, 40 days after a boost immunization, the presence of CD4 + help enhanced antigen‐specific IFN‐γ‐secreting CD8 + T cells and tumor protection in mice challenged with B16.OVA. Long‐term CD8 responses were equally enhanced by antigen‐specific and universal CD4 help. In addition, immunization with AntpOVA significantly delayed growth of B16.OVA tumors in mice in a tumor therapy model.