HHD transgenic mice which express HLA‐A2.1 monochain molecules in a H‐2 class I^– context have an improved capacity to develop HLA‐A2.1‐restricted cytotoxic T lymphocyte (CTL) responses as compared with classical A2.1/K^b transgenic mice, which express heterodimeric HLA‐A2.1 molecules in a H‐2 class I wild‐type context. A detailed TCR analysis of HLA‐A2.1‐restricted CD8⁺ T cells educated and mobilized in both strains of mice was undertaken. Focusing on TCR β chains, comparative PCR analysis of naive and immune CD8⁺ T cell repertoires were performed. In spite of lower cell surface expression of HLA class I molecules and lower overall number of CD8⁺ T cells, HHD mice educate a qualitatively normally diversified CD8⁺ T cell repertoire and mobilize a larger variety of CD8⁺ T cells in response to HLA‐A2.1‐restricted antigens compared with A2.1/K^b mice. These observations provide the molecular bases accounting for the fact that HHD mice represent the most versatile animal model currently available for preclinical studies of HLA‐A2.1‐restricted CTL responses.