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Updated: Aug 11, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
Published on: October 8, 2012
Negative selection imparts peptide specificity to the mature T cell repertoire
Eric S Huseby1, Frances Crawford, Janice White
1Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
The T cell alphabeta receptor (TCR) recognizes foreign peptide antigens bound to proteins encoded in the MHC. The MHC portion of this complex contributes much to the footprint of the TCR on the ligand, yet T cells are usually very specific for individual foreign peptides. Here, we show that the development of peptide-specific T cells is not intrinsic to thymocytes that undergo thymic-positive selection but is an outcome of eliminating, through negative selection, thymocytes bearing TCRs with extensive peptide cross-reactivity. Hence, thymic-negative selection imposes peptide specificity on the mature T cell repertoire.
The T cell alphabeta receptor (TCR) recognizes foreign peptide antigens bound to proteins encoded in the MHC. The MHC portion of this complex contributes much to the footprint of the TCR on the ligand, yet T cells are usually very specific for individual foreign peptides. Here, we show that the development of peptide-specific T cells is not intrinsic to thymocytes that undergo thymic-positive selection but is an outcome of eliminating, through negative selection, thymocytes bearing TCRs with extensive peptide cross-reactivity. Hence, thymic-negative selection imposes peptide specificity on the mature T cell repertoire.
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