Selection of Thymocytes Expressing Transgenic TCR Specific for a Minor Histocompatibility Antigen, H60.
- Author:
Ji Min JU
1
;
Min Bum KIM
;
Su Jeong RYU
;
Joo Young KIM
;
Jun CHANG
;
Eun Young CHOI
Author Information
- Publication Type:Original Article
- Keywords: TCR transgenic mouse; H60; Peptide variants; Negative selection
- MeSH: Actins; Animals; Histocompatibility Antigens*; Histocompatibility*; Mice; Mice, Transgenic; Minor Histocompatibility Antigens; Peptides; T-Lymphocytes; Thymocytes*; Thymus Gland; Transplantation, Homologous
- From:Immune Network 2015;15(5):222-231
- CountryRepublic of Korea
- Language:English
- 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.
