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 b chains, comparative PCR analysis of

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... 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 diversi®ed 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.