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T Cell Development ? ? ? ?? ? ?
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Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell repertoire –Transplant experiments
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Shaping the T cell repertoire
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What are thymocytes doing? MigratingMigrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selection
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What are thymocytes doing? Migrating Contacting stromal cellsContacting stromal cells Changing phenotype Expressing TCRs Undergoing selection
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Thymocyte:stromal cell interactions
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What are thymocytes doing? Migrating Contacting stromal cells Changing phenotypeChanging phenotype Expressing TCRs Undergoing selection
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T Cell Development in the Thymus
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What are thymocytes doing? Migrating Contacting stromal cells Changing phenotype Expressing TCRsExpressing TCRs Undergoing selection
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T Cell Development in the Thymus
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What are thymocytes doing? Migrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selectionUndergoing selection
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T and B cell receptors
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Based on specificity of TCR Produces “central tolerance” to self antigens Produces T cell repertoire biased toward self MHC + peptide specificities Consists of 3 levels of selection –Positive Selection –Negative Selection –Death by neglect Thymic Selection
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Positive selection
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Negative selection
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Thymic Selection
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CD4/CD8 lineage commitment
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