T Cell Development Role of the thymus in

T Cell Development ? ? ?

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? • • • Migrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selection

What are thymocytes doing? • • • Migrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selection

Thymocyte: stromal cell interactions

What are thymocytes doing? • • • Migrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selection

T Cell Development in the Thymus

What are thymocytes doing? • • • Migrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selection

T Cell Development in the Thymus

What are thymocytes doing? • • • Migrating Contacting stromal cells Changing phenotype Expressing TCRs Undergoing selection

T and B cell receptors

Thymic Selection • 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

Positive selection

Positive selection

Positive selection

Negative selection

Thymic Selection

CD 4/CD 8 lineage commitment