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Peptide-MHC class II complex stability governs CD4 T cell clonal selection.

TitlePeptide-MHC class II complex stability governs CD4 T cell clonal selection.
Publication TypeJournal Article
Year of Publication2010
AuthorsBaumgartner, CK, Ferrante, A, Nagaoka, M, Gorski, J, Malherbe, LP
JournalJ Immunol
Volume184
Issue2
Pagination573-81
Date Published2010 Jan 15
ISSN1550-6606
KeywordsAnimals, Autoimmunity, CD4-Positive T-Lymphocytes, Clone Cells, Half-Life, Histocompatibility Antigens Class II, Immunization, Mice, Mutation, Peptides, Protein Stability
Abstract

The clonal composition of the T cell response can affect its ability to mediate infection control or to induce autoimmunity, but the mechanisms regulating the responding TCR repertoire remain poorly defined. In this study, we immunized mice with wild-type or mutated peptides displaying varying binding half-lives with MHC class II molecules to measure the impact of peptide-MHC class II stability on the clonal composition of the CD4 T cell response. We found that, although all peptides elicited similar T cell response size on immunization, the clonotypic diversity of the CD4 T cell response correlated directly with the half-life of the immunizing peptide. Peptides with short half-lives focused CD4 T cell response toward high-affinity clonotypes expressing restricted public TCR, whereas peptides with longer half-lives broadened CD4 T cell response by recruiting lower-affinity clonotypes expressing more diverse TCR. Peptides with longer half-lives did not cause the elimination of high-affinity clonotypes, and at a low dose, they also skewed CD4 T cell response toward higher-affinity clonotypes. Taken collectively, our results suggest the half-life of peptide-MHC class II complexes is the primary parameter that dictates the clonotypic diversity of the responding CD4 T cell compartment.

DOI10.4049/jimmunol.0902107
Alternate JournalJ. Immunol.
PubMed ID20007533
PubMed Central IDPMC2975033
Grant ListJ 2851-B19 / / Austrian Science Fund FWF / Austria
U19 A162627 / / PHS HHS / United States
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