Recognition of a specific self-peptide: self-MHC class II complex is critical for positive selection of thymocytes expressing the D10 TCR.

TitleRecognition of a specific self-peptide: self-MHC class II complex is critical for positive selection of thymocytes expressing the D10 TCR.
Publication TypeJournal Article
Year of Publication2003
AuthorsDao, T, J Blander, M, Sant'Angelo, DB
JournalJ Immunol
Volume170
Issue1
Pagination48-54
Date Published2003 Jan 01
ISSN0022-1767
KeywordsAlleles, Animals, Arginine, Autoantigens, Cell Differentiation, Cell Line, Complementarity Determining Regions, Conalbumin, Down-Regulation, Epitopes, T-Lymphocyte, Glycine, Histocompatibility Antigens Class II, Leucine, Lymphocyte Count, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Peptides, Point Mutation, Receptors, Antigen, T-Cell, alpha-beta, Serine, T-Lymphocyte Subsets, Thymus Gland, Transgenes
Abstract

We examined the specificity of positive and negative selection by using transgenic mice carrying a variant of the D10 TCR. We demonstrate that a point mutation at position 51 within the CDR2alpha segment significantly reduces the avidity of this TCR for its cognate ligand, but does not impact recognition of nonself MHC class II molecules. Although structural studies have suggested that this TCR site interacts with the MHC class II beta-chain, the avidity of this TCR for its ligand and the function of the T cell can be reconstituted by a point mutation in the bound antigenic peptide. These data demonstrate that the bound peptide can indirectly alter TCR interactions by influencing MHC structure. Remarkably, reducing the avidity of this TCR for a specific antigenic peptide-MHC ligand has a dramatic impact on thymic selection. Positive selection of thymocytes expressing this TCR is nearly completely blocked, whereas negative selection on allogenic MHC class II molecules remains intact. Therefore, the recognition of self that promotes positive selection of the D10 TCR is highly peptide-specific.

Alternate JournalJ. Immunol.
PubMed ID12496382
Grant ListR01 AI-41574 / AI / NIAID NIH HHS / United States
T32 CA 09149 / CA / NCI NIH HHS / United States