The self-antigen Melan-A/MART-1 is frequently involved in T-cell responses against malignant melanoma. The use of fluorescent tetramers incorporating the immunodominant Melan-A/MART-1 peptide has provided new insights into HLA-A2-restricted T-cell responses against this antigen in cancer patients and in healthy individuals. Direct evidence has been provided that a large Melan-A/MART-1-specific CD8 T-cell pool is generated during thymic selection. Although several other examples of naive self-peptide-specific T-cell repertoires are known, this is the only one directly accessible to analysis in healthy individuals