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Positive selection of self-MHC-reactive T cells by individual peptide-MHC class II complexes.


ABSTRACT: 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-1-A(b)(A(b)) 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.

SUBMITTER: Barton GM 

PROVIDER: S-EPMC124507 | biostudies-literature | 2002 May

REPOSITORIES: biostudies-literature

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Positive selection of self-MHC-reactive T cells by individual peptide-MHC class II complexes.

Barton Gregory M GM   Beers Courtney C   deRoos Paul P   Eastman Susan R SR   Gomez Marcela E ME   Forbush Katherine A KA   Rudensky Alexander Y AY  

Proceedings of the National Academy of Sciences of the United States of America 20020501 10


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-1-A(b)(A(b)) 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-ty  ...[more]

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