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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.

Original publication

DOI

10.1093/intimm/dxn066

Type

Journal article

Journal

Int Immunol

Publication Date

08/2008

Volume

20

Pages

1087 - 1096

Keywords

Antigens, Bacterial, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Cancer Vaccines, Cells, Cultured, Clone Cells, Cross-Priming, Cytotoxicity, Immunologic, Humans, Immunologic Memory, Immunophenotyping, MART-1 Antigen, Melanoma, Mycobacterium tuberculosis, Neoplasm Proteins, Peptides, T-Cell Antigen Receptor Specificity, Tuberculosis, Pulmonary