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International Immunology Advance Access originally published online on June 23, 2008
International Immunology 2008 20(8):1087-1096; doi:10.1093/intimm/dxn066
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Characterization of Melan-A reactive memory CD8+ T cells in a healthy donor

Verena Voelter1, Nathalie Rufer1, Severine Reynard1, Gilbert Greub2, Roger Brookes3, Philippe Guillaume4, Frederic Grosjean4, Theres Fagerberg5, Olivier Michelin1,5, Sarah Rowland-Jones3, Clemencia Pinilla6, Serge Leyvraz1, Pedro Romero4 and Victor Appay1,7

1 Multidisciplinary Oncology Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
2 Center for Research on Intracellular Bacteria, Microbiology Institute, CHUV and University of Lausanne, Lausanne, Switzerland
3 Medical Research Council Laboratories, Banjul, The Gambia
4 Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, Switzerland
5 Swiss Institute for Bioinformatics, Génopode, Lausanne, Switzerland
6 Torrey Pines Institute for Molecular Studies, San Diego, CA, USA
7 Cellular Immunology Laboratory, INSERM U543, Avenir Group, Hôpital Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris 6, Paris, France

Correspondence to: V. Appay; E-mail: victor.appay{at}chups.jussieu.fr

Melan-A specific CD8+ T cells are thought to play an important role against the development of melanoma. Their in vivo expansion is often observed with advanced disease. In recent years, low levels of Melan-A reactive CD8+ T cells have also been found in HLA-A2 healthy donors, but these cells harbor naive characteristics and are thought to be mostly cross-reactive for the Melan-A antigen. Here, we report on a large population of CD8+ T cells reactive for the Melan-A antigen, identified in one donor with no evidence of melanoma. Interestingly, this population is oligoclonal and displays a clear memory phenotype. However, a detailed study of these cells indicated that they are unlikely to be directly specific for melanoma, so that their in vivo expansion may have been driven by an exogenous antigen. Screening of a Melan-A cross-reactive peptide library suggested that these cells may be specific for an epitope derived from a Mycobacterium protein, which would provide a further example of CD8+ T cell cross-reactivity between a pathogen antigen and a tumor antigen. Finally, we discuss potential perspectives regarding the role of such cells in heterologous immunity, by influencing the balance between protective immunity and pathology, e.g. in the case of melanoma development.

Keywords: cross-reactivity, melanoma, Mycobacterium, T lymphocytes, tumor immunity

Transmitting editor: T. Hünig

Received 4 February 2008, accepted 27 May 2008.


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