title: Selection of Thymocytes Expressing Transgenic TCR Specific for a Minor Histocompatibility Antigen, H60.
abstract: Minor histocompatibility antigens are MHC-bound peptides and contribute to the generation of allo-responses after allogeneic transplantation. H60 is a dominant minor H antigen that induces a strong CD8 T-cell response in MHC-matched allogeneic transplantation settings. Here, we report establishment of a TCR transgenic mouse line named J15, wherein T cells express TCRs specific for H60 in complex with H-2K(b), and different fates of the thymocytes expressing J15 TCRs in various thymic antigenic environments. Thymocytes expressing the J15 TCRs were positively selected and differentiated into CD8(+) single positive (SP) cells in the thymus of C57BL/6 mice, wherein the cognate antigen H60 is not expressed. However, thymocytes were negatively selected in thymus tissue where H60 was transgenically expressed under the control of the actin promoter, with double-positive stages of cells being deleted. Despite the ability of the H60H peptide (LTFHYRNL) variant to induce cytotoxic activity from H60-specific CTL lines at ~50% of the activity induced by normal H60 peptides (LTFNYRNL), J15-expressing thymocytes were positively selected in the thymus where the variant H60H was transgenically expressed. These results demonstrate that a single amino-acid change in the H60 epitope peptide influences the fate of thymocytes expressing the cognate TCR.
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Ju
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Min Bum
authors.initials: MB
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Su Jeong
authors.initials: SJ
authors.lastname: Ryu
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Korea.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Choi
keywords: H60; Negative selection; Peptide variants; TCR transgenic mouse