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Updated: Apr 5, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
Published on: October 8, 2012
TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+)
Kensuke Takada1, Francois Van Laethem2, Yan Xing3
1Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima, Japan.
Abstract:
In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8(+) T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8(+) T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8(+) T cells in the periphery.
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