Thymocyte - Events During Maturation

In order to pass the β-selection checkpoint, the β chain of the T cell receptor rearranged by the thymocyte must retain the structural properties allowing it to be presented on the surface of the thymocyte with pre-TCRα. This eliminates thymocytes with gross defects introduced into the T cell receptor by gene rearrangement.

In order to be positively-selected, thymocytes will have to interact with several cell surface molecules, MHC, to ensure reactivity and specificity.

Positive selection selects cells with a T cell receptor able to bind MHC class I or II molecules with at least a weak affinity. This eliminates (by a process called "death by neglect") those T cells which would be non-functional due to an inability to bind MHC.

Negative selection is the active induction of apoptosis in thymocytes with a high affinity for self peptides or MHC. This eliminates cells which would direct immune responses towards self-proteins in the periphery. Negative selection is not 100% effective, some autoreactive T cells escape thymic censorship, and are released into the circulation.

Additional mechanisms of tolerance active in the periphery exist to silence these cells such as anergy, deletion, and regulatory T cells. If these peripheral tolerance mechanisms also fail, autoimmunity may arise.