The self peptide annexin II (208-223) presented by dendritic cells sensitizes autologous CD4+ T lymphocytes to recognize melanoma cells.
Annexin II is known to be over-expressed in different types of tumours. We show here that annexin II protein is expressed by melanoma cell lines in various amounts, consistent with previous findings that an annexin II (208-223) peptide could be eluted from isolated HLA-DR molecules of a constitutively MHC class II-positive melanoma line. T cells sensitized to annexin II (208-223) in vitro using peptide-pulsed autologous dendritic cells responded only to the lines which overexpressed annexin II, in a peptide-specific, HLA-DR-restricted fashion. These CD4+ T cells proliferated strongly and secreted large amounts of type 1 cytokines in response to annexin II (208-223) peptide or annexin II protein-positive melanoma cell lines. These results demonstrate that the annexin II (208-223) peptide, corresponding to a non-mutated sequence of a normal protein, induces antigen-specific T cells which can respond to melanoma cells over-expressing the annexin II molecule. This peptide may therefore be useful in immunotherapy for recruiting CD4+ type 1 helper cells active locally in the tumour environment.
University of Tübingen, Second Department of Internal Medicine, Zentrum für Medizinische Forschung ZMF, Germany.
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S
Heinzel
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Rea
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Offringa
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Pawelec
D000368:Aged; D000818:Animals; D017306:Annexin A2 / Q000276:immunology* / Q000378:metabolism; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007114:Immunization; D016753:Interleukin-10 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008545:Melanoma / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology; D009363:Neoplasm Proteins / Q000276:immunology; D010446:Peptide Fragments / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017306:Annexin A2; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor