Immunity to tumor differentiation antigens, such as melanoma antigen recognized by T cells 1 (MART‐1), has been comprehensively studied. Intriguingly, CD8⁺ T cells specific for the MART‐1_26(27)‐35 epitope in the context of HLA‐A0201 are about 100 times more abundant compared with T cells specific for other tumor‐associated antigens. Moreover, MART‐1‐specific CD8⁺ T cells show a highly biased usage of the Vα‐region gene TRAV12–2. Here, we provide independent support for this notion, by showing that the combinatorial pairing of different TCRα‐ and TCRβ‐ chains derived from HLA‐A2–MART‐1_26–35‐specific CD8⁺ T‐cell clones is unusually permissive in conferring MART‐1 specificity, provided the CDR1α TRAV12–2 region is used. Whether TCR bias alone accounts for the unusual abundance of HLA‐A2–MART‐1_26–35‐specific CD8⁺ T cells has remained conjectural. Here, we provide an alternative explanation: misinitiated transcription of the MART‐1 gene resulting in truncated mRNA isoforms leads to lack of promiscuous transcription of the MART‐1_26–35 epitope in human medullary thymic epithelial cells and, consequently, evasion of central self‐tolerance toward this epitope. Thus, biased TCR usage and leaky central tolerance might act in an independent and additive manner to confer high frequency of MART‐1_26–35‐specific CD8⁺ T cells.