1. T Cell Development ? ? ? ?? ? ?

3. Role of the thymus in T cell development Required for T cell development –Neonatal thymectomy –Nude mice Shapes T cell repertoire –Transplant experiments

4. Shaping the T cell repertoire

5. What are thymocytes doing? MigratingMigrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selection

7. What are thymocytes doing? Migrating Contacting stromal cellsContacting stromal cells Changing phenotype Expressing TCRs Undergoing selection

8. Thymocyte:stromal cell interactions

9. What are thymocytes doing? Migrating Contacting stromal cells Changing phenotypeChanging phenotype Expressing TCRs Undergoing selection

10. T Cell Development in the Thymus

11. What are thymocytes doing? Migrating Contacting stromal cells Changing phenotype Expressing TCRsExpressing TCRs Undergoing selection

12. T Cell Development in the Thymus

15. What are thymocytes doing? Migrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selectionUndergoing selection

16. T and B cell receptors

17. 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

18. Positive selection

21. Negative selection

22. Thymic Selection

24. CD4/CD8 lineage commitment