title: Relationship between Poor Immunogenicity of HLA-A2-Restricted Peptide Epitopes and Paucity of Naïve CD8(+) T-Cell Precursors in HLA-A2-Transgenic Mice.
abstract: We examined the immunogenicity of H-2 class I-restricted and HLA-A2-restricted epitopes through peptide immunization of HLA-A2-transgenic mice that also express mouse H-2 class I molecules. All four of the tested epitopes restricted by H-2 class I robustly elicited T-cell responses, but four of seven epitopes restricted by HLA-A2 did not induce T-cell responses, showing that HLA-A2-restricted peptide epitopes tend to be poorly immunogenic in HLA-A2-transgenic mice. This finding was confirmed in HLA-A2-transgenic mice infected with a recombinant vaccinia virus expressing hepatitis C virus proteins. We examined the precursor frequency of epitope-specific naïve CD8(+) T cells in HLA-A2-transgenic and conventional C57BL/6 mice and found that the poor immunogenicity of HLA-A2-restricted peptide epitopes is related to the paucity of naïve CD8(+) T-cell precursors in HLA-A2-transgenic mice. These results provide direction for the improvement of mouse models to study epitope repertoires and the immunodominance of human T-cell responses.
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea. ; Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon 301-721, Korea.
authors.forename: Yoon Seok
authors.initials: YS
authors.lastname: Choi
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon 305-701, Korea.
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
keywords: CD8+ T cells; HLA-A2; Major histocompatibility complex class I; Naïve T cell precursor; T cell epitope; T cell immunogenicity