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Unformatted text preview: TCell Development Figure 51 Figure 52 Figure 53 In the thymic cortex, and chain genes Early Stages of TCell Differentiation begin to rearrange. If the chain gene rearranges successfully, the chain gene begins rearrangement. If the chain gene and the chain gene rearrange productively, no further gene rearrangement occurs and the cell remains a Tcell. If the chain gene and the chain gene Early Stages of TCell Differentiation do not rearrange productively, chain rearrangement continues. A productive chain rearrangement results in the expression of the chain on the cell surface in a complex with CD3 and an invariant molecule known as pT. This complex makes up the preTcell Early Stages of TCell Differentiation receptor. Tcells bearing these receptors are called preTcells. Signaling through the preTcell receptor stops further gene rearrangement. Also expression of pT is downregulated, genes begin to rearrange and cell proliferation occurs The next important cell in the Tcell Late Stages of TCell Differentiation lineage is the double positive Tcell. This cell expresses both CD4 and CD8 along with the Tcell receptor. This cell type is the most common in the thymus of young mammals. These double positive Tcells next undergo thymic selection. Figure 518 The TCR of doublepositive T cells Positive Selection (Thymic Education) interacts with MHC molecules expressed on epithelial cells in the thymic cortex. Doublepositive T cells that can not interact with the thymic epithelial cells die by apoptosis. Thus Tcells with receptors that do not recognize self MHC are eliminated. Positive Selection (Thymic Education) Tcells that do interact proliferate and expand in numbers. As a result of positive selection Tcells become "educated" to the MHC molecules expressed by the thymic epithelium. For the rest of its life the Tcell will only recognize antigen when it is associated with the same MHC molecules as those expressed on the thymic epithelium. Negative Selection (Central Tolerance) To prevent Tcells with potential reactivity to self antigens from leaving the thymus the double positive Tcells undergo a process known as negative selection. The Tcells interact with dendritic cells in the thymus. The dendritic cells are presenting self peptides associated with MHC class I and class II on their surface. Tcells with TCRs that recognize self Negative Selection (Central Tolerance) peptides plus MHC with high affinity are deleted by apoptosis. Thus negative selection removes T cells that could react against self antigens. After negative selection Tcells are "tolerant" of self antigen. At least of self antigen that can be presented in the thymus. Figure 512 Figure 56 Figure 57 Figure 58 Figure 59 Figure 510 Figure 511 Figure 514 Figure 516 Figure 519 ...
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- Spring '06