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KMID : 0923620150150050222
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Immune Network
2015 Volume.15 No. 5 p.222 ~ p.231
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Selection of Thymocytes Expressing Transgenic TCR Specific for a Minor Histocompatibility Antigen, H60
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:Ju Ji-Min
:Kim Min Bum/:Ryu Su-Jeong/:Choi Eun-Young/:Kim Joo-Young/:Chang Jun
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Abstract
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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-2Kb, 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.
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KEYWORD
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TCR transgenic mouse, H60, Peptide variants, Negative selection
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