Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 10, Pages 6937-6942Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.102645699
Keywords
thymus; CD4 T cells; development; T cell specificity; mice
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Funding
- NIAID NIH HHS [AI34206, R01 AI034206, R37 AI034206] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007270, T32 GM07270] Funding Source: Medline
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If T cells require specific interactions with MHC-bound peptides during positive selection, then the specificities of T cells selected by one peptide should be distinct from those selected by another. We have examined positive selection of CD4 T cells in four strains of mice, each overexpressing a different peptide-l-All(Ab) complex. We show that a subset of CD4 T cells is selected by the overexpressed peptide and that the specificities of the CD4 T cells, as measured by reactivity to wild-type antigen-presenting cells, vary greatly depending on which peptide is overexpressed. These differences in specificity are mediated through positive selection not negative selection. Each of the four peptide-A(b) complexes appears to adopt a different conformation, and these differences correlate with the differences in reactivity. Our results suggest that individual peptide-MHC complexes positively select different subsets of self-MHC-reactive T cells and that the conformation of the peptide-MHC complex may contribute to this process.
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