Positive selection of the T-Cell repertoire is affected by mutations in the peptide-binding site of MHC class I molecules

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Abstract

H-2Kb mutant molecules (H-2Kbm) and the H-2Kb-restricted response to OVA and VSV N peptides were used to investigate the influence of polymorphism of structurally defined regions of the MHC class I molecules on intrathymic positive selection of the T-cell repertoire. We show that the positive selection of the T-cell repertoire in the thymus requires the self-peptide to be present in the MHC antigenbinding site. A correlation between the ability of four MHC molecules to present antigenic peptide and to positively select T cells specific for it was noted. The self-peptides involved in positive selection may therefore mimic the foreign peptide during intrathymic selection. A structural correlate of this mimicry may be a similar or identical binding requirement for the antigen-binding pocket(s)/residues of the MHC peptide-binding site.

Original languageEnglish (US)
Pages (from-to)16-24
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume681
Publication statusPublished - 1993
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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