Negative selection imparts peptide specificity to the mature T cell repertoire

doi:10.1073/pnas.1934636100

Negative selection imparts peptide specificity to the mature T cell repertoire

^*Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; and Departments of ^†Medicine, ^‡Pharmacology, and ^§Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80262

Contributed by Philippa Marrack, July 22, 2003

Abstract

The T cell αβ 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.

Footnotes

↵ ¶ To whom correspondence should be addressed at: Howard Hughes Medical Institute, National Jewish Medical and Research Center, K512 Goodman Building, 1400 Jackson Street, Denver, CO 80220. E-mail: marrackp{at}njc.org.
Abbreviations: BM, bone marrow; DC, dendritic cell; TCR, T cell receptor; APC, antigen-presenting cell; SP-APC, single-peptide APC; MCC, moth cytochrome c; Ii, invariant chain.