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