page_title: Thymocyte
section_title: β-selection
hierarchical_section_title: Thymocyte / Events during maturation / β-selection
context_page_description: A Thymocyte is an immune cell present in the thymus, before it undergoes transformation into a T cell. Thymocytes are produced as stem cells in the bone marrow and reach the thymus via the blood. Thymopoiesis describes the process which turns thymocytes into mature T cells according to either negative or positive selection. This selection process is vitally important in shaping the population of thymocytes into a peripheral pool of T cells that are able to respond to foreign pathogens but remain tolerant towards the body's own antigens. Positive selection selects cells which are able to bind MHC class I or II molecules with at least a weak affinity. This eliminates those T cells which would be non-functional due to an inability to bind MHC. Negative selection destroys 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, and some autoreactive T cells escape and are released into the circulation. Additional mechanisms of peripheral tolerance exist to silence these cells, but if these fail, autoimmunity may arise.
context_section_description: The ability of T cells to recognize foreign antigens is mediated by the T cell receptor (TCR), which is a surface protein able to recognize short protein sequences (peptides) that are presented on MHC. The purpose of thymocyte development is to produce mature T cells with a diverse array of functional T cell receptors, through the process of TCR gene rearrangement.
  Unlike most genes, which have a stable sequence in each cell which expresses them, the T cell receptor is made up of a series of alternative gene fragments. In order to create a functional T cell receptor, the double negative thymocytes use a series of DNA-interacting enzymes to clip the DNA and bring separate gene fragments together. The outcome of this process is that each T cell receptor has a different sequence, due to different choice of gene fragments and the errors introduced during the cutting and joining process (see section on V(D)J recombination for more information on TCR rearrangement). The evolutionary advantage in having a large number of unique T cell receptors is that each T cell is capable of recognizing a different peptide, providing a defense against rapidly evolving pathogens.
  TCR rearrangement occurs in two steps. First the TCRβ chain is rearranged at the DN3 stage of T cell development. The TCRβ chain is paired with the pre-Tα to generate the pre-TCR. The cellular disadvantage in the rearrangement process is that many of the combinations of the T cell receptor gene fragments are non-functional. To eliminate thymocytes which have made a non-functional T cell receptor, only cells that have successfully rearranged the beta chain to produce a functional pre-TCR are allowed to develop beyond the DN3 stage. Cells that fail to produce a functional pre-TCR are eliminated by apoptosis. This process is referred to as the beta-selection checkpoint. Successful beta-selection requires that TCRβ is produced, TCRβ is capable of pairing with pre-Tα to generate the pre-TCR, and that the pre-TCR can interact on the cell surface with the TCR signalling proteins.
  Following β-selection thymocytes generate CD4+CD8+ double positive cells, which then undergo TCRα rearrangement, resulting in completely assembled TCR.
caption: Minute structure of thymus.
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