alpha v beta3-dependent cross-presentation of matrix metalloproteinase-2 by melanoma cells gives rise to a new tumor antigen.

Abstract	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.
Authors	Emmanuelle Godefroy, Agnes Moreau-Aubry, Elisabeth Diez, Brigitte Dreno, Francine Jotereau, Yannick Guilloux
Journal	The Journal of experimental medicine (J Exp Med) Vol. 202 Issue 1 Pg. 61-72 (Jul 04 2005) ISSN: 0022-1007 [Print] United States
PMID	15998788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, Neoplasm DNA, Complementary Epitopes HLA-A Antigens HLA-A*02:01 antigen HLA-A2 Antigen Integrin alphaVbeta3 Matrix Metalloproteinase 2 Proteasome Endopeptidase Complex
Topics	Animals Antigen Presentation Antigens, Neoplasm (metabolism) Base Sequence COS Cells Cell Line Cell Line, Tumor Chlorocebus aethiops Clathrin-Coated Vesicles (enzymology, immunology) DNA, Complementary (genetics) Epitopes (metabolism) HLA-A Antigens (metabolism) HLA-A2 Antigen Humans Integrin alphaVbeta3 (metabolism) Matrix Metalloproteinase 2 (genetics, immunology, metabolism) Melanoma (enzymology, immunology) Proteasome Endopeptidase Complex (metabolism) T-Lymphocytes, Cytotoxic (immunology)

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