alpha v beta3-dependent cross-presentation of matrix metalloproteinase-2 by melanoma cells gives rise to a new tumor antigen.
A large array of antigens that are recognized by tumor-specific T cells has been identified and shown to be generated through various processes. We describe a new mechanism underlying T cell recognition of melanoma cells, which involves the generation of a major histocompatibility complex class I-restricted epitope after tumor-mediated uptake and processing of an extracellular protein--a process referred to as cross-presentation-which is believed to be restricted to immune cells. We show that melanoma cells cross-present, in an alpha v beta3-dependent manner, an antigen derived from secreted matrix metalloproteinase-2 (MMP-2) to human leukocyte antigen A*0201-restricted T cells. Because MMP-2 activity is critical for melanoma progression, the MMP-2 peptide should be cross-presented by most progressing melanomas and represents a unique antigen for vaccine therapy of these tumors.
Institut National de la Santé et de la Recherche Médicale, Unité 601, Nantes, France.
Emmanuelle
E
Godefroy
Agnes
A
Moreau-Aubry
Elisabeth
E
Diez
Brigitte
B
Dreno
Francine
F
Jotereau
Yannick
Y
Guilloux
D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000378:metabolism*; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D022163:Clathrin-Coated Vesicles / Q000201:enzymology / Q000276:immunology; D018076:DNA, Complementary / Q000235:genetics; D000939:Epitopes / Q000378:metabolism; D015234:HLA-A Antigens / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000201:enzymology* / Q000276:immunology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000951:Antigens, Neoplasm; D018076:DNA, Complementary; D000939:Epitopes; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D039302:Integrin alphaVbeta3; D020778:Matrix Metalloproteinase 2; D046988:Proteasome Endopeptidase Complex