The Journal of Experimental Medicine
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Published 5 July 2005. doi:10.1084/jem.20042138
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 1, 61-72
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ARTICLE

 {alpha}vß3-dependent cross-presentation of matrix metalloproteinase–2 by melanoma cells gives rise to a new tumor antigen

Emmanuelle Godefroy1, Agnes Moreau-Aubry1,3, Elisabeth Diez1, Brigitte Dreno1,2, Francine Jotereau1,3, and Yannick Guilloux1,3

1 Institut National de la Santé et de la Recherche Médicale, Unité 601
2 Unit of Skin Cancer, Centre Hospitalier Régional Hotel Dieu, 44093 Nantes Cedex 1, France
3 Faculté des Sciences et Techniques de Nantes, 44322 Nantes Cedex 3, France

CORRESPONDENCE Francine Jotereau: jotereau{at}nantes.inserm.fr

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}vß3-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.

Abbreviations used: MMP; matrix metalloproteinase; MT1, membrane type 1; TIL, tumor-infiltrating lymphocyte; TPP, tripeptidyl peptidase.


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