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
Shaping the T cell repertoire
What are thymocytes doing?
• MigratingMigrating
• Contacting stromal cells
• Changing phenotype
• Expressing TCRs
• Undergoing selection
What are thymocytes doing?
• Migrating
• Contacting stromal cellsContacting stromal cells
• Changing phenotype
• Expressing TCRs
• Undergoing selection
Thymocyte:stromal cell interactions
What are thymocytes doing?
• Migrating
• Contacting stromal cells
• Changing phenotypeChanging phenotype
• Expressing TCRs
• Undergoing selection
T Cell Development in the Thymus
What are thymocytes doing?
• Migrating
• Contacting stromal cells
• Changing phenotype
• Expressing TCRsExpressing TCRs
• Undergoing selection
T Cell Development in the Thymus
What are thymocytes doing?
• Migrating
• Contacting stromal cells
• Changing phenotype
• Expressing TCRs
• Undergoing selectionUndergoing selection
T and B cell receptors
• 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
Positive selection
Positive selection
Positive selection
Negative selection
Thymic Selection
CD4/CD8 lineage commitment
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