Positive Selection Ensures MHC Restriction

Positive selection takes place in the cortical region of the thymus and involves the interaction of immature thymocytes with cortical epithelial cells (Figure 10-5). There is evidence that the T-cell receptors on thymocytes tend to cluster with

T-cell precursor

Rearrangement of TCR genes

Immature thymocyte

Positive selection of cells whose receptor binds MHC molecules

Class I and/or class II MHC molecules

T-cell precursor

Immature thymocyte

Rearrangement of TCR genes

Positive selection of cells whose receptor binds MHC molecules

CD8 /CD3

T-cell receptor CD4

Death by apoptosis of cells that do not interact with MHC molecules

Class I and/or class II MHC molecules

Mhc Restriction Cells

Th cell Tc cell

Mature CD4+ or CD8+ T lymphocytes

Death by apoptosis of cells that do not interact with MHC molecules

Negative selection and death of cells with high-affinity receptors for self-MHC or self-MHC + self-antigen

Th cell Tc cell

Mature CD4+ or CD8+ T lymphocytes

Negative selection and death of cells with high-affinity receptors for self-MHC or self-MHC + self-antigen

Mhc Positve Selection

Dendritic cell

Positive and negative selection of thymocytes in the thymus. Thymic selection involves thymic stromal cells (epithelial cells, dendritic cells, and macrophages), and results in mature T cells that are both self-MHC restricted and self-tolerant.

Dendritic cell

FIGURE 10-5

Positive and negative selection of thymocytes in the thymus. Thymic selection involves thymic stromal cells (epithelial cells, dendritic cells, and macrophages), and results in mature T cells that are both self-MHC restricted and self-tolerant.

MHC molecules on the cortical cells at sites of cell-cell contact. Some researchers have suggested that these interactions allow the immature thymocytes to receive a protective signal that prevents them from undergoing cell death; cells whose receptors are not able to bind MHC molecules would not interact with the thymic epithelial cells and consequently would not receive the protective signal, leading to their death by apoptosis.

During positive selection, the RAG-1, RAG-2, and TdT proteins required for gene rearrangement and modification continue to be expressed. Thus each of the immature thymocytes in a clone expressing a given p chain have an opportunity to rearrange different TCR a-chain genes, and the resulting TCRs are then selected for self-MHC recognition. Only those cells whose ap TCR heterodimer recognizes a self-MHC molecule are selected for survival. Consequently, the presence of more than one combination of ap TCR chains among members of the clone is important because it increases the possibility that some members will "pass" the test for positive selection. Any cell that manages to rearrange an a chain that allows the resulting ap TCR to recognize self-MHC will be spared; all members of the clone that fail to do so will die by apoptosis within 3 to 4 days.

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