negative regulation of positive thymic T cell selection

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of positive thymic T cell selection. [GOC:TermGenie, PMID:22080863]

Negative regulation of positive thymic T cell selection is a critical process that ensures the proper development and maturation of T cells in the thymus. It involves the downregulation of signals that promote the survival and differentiation of T cells that recognize self-antigens with too high affinity. This ensures that the immune system does not target and destroy its own tissues. The process involves several key steps:

1. **Thymic T cell selection:** During their development in the thymus, T cells undergo a process called selection, where they are tested for their ability to recognize and bind to self-antigens presented by thymic epithelial cells. T cells that recognize self-antigens with too high affinity are eliminated through a process called negative selection, while those that recognize self-antigens with low affinity survive and mature.

2. **Signal transduction pathways:** The recognition of self-antigens by T cell receptors (TCRs) triggers downstream signaling pathways that lead to the activation of transcription factors and the expression of genes involved in T cell survival, proliferation, and differentiation. In the case of negative selection, these pathways are often downregulated or inhibited.

3. **Inhibitory receptors:** Several inhibitory receptors, such as CTLA-4 and PD-1, are expressed on T cells and can bind to ligands on antigen-presenting cells. These interactions trigger signaling pathways that inhibit TCR-mediated activation and promote T cell anergy or apoptosis.

4. **Apoptosis:** If the signals that promote T cell survival are sufficiently downregulated, the T cell undergoes programmed cell death, or apoptosis.

5. **T cell anergy:** In some cases, T cells may not undergo apoptosis but instead become anergic, meaning they are unable to respond to subsequent stimulation by their cognate antigen.

6. **Regulatory T cells:** Another important mechanism of negative regulation is the development of regulatory T cells (Tregs). These cells express the transcription factor Foxp3 and are specialized to suppress the activity of other T cells, including those that may have escaped negative selection.

Overall, negative regulation of positive thymic T cell selection is a complex and tightly regulated process that ensures the development of a self-tolerant T cell repertoire. It involves a variety of mechanisms, including inhibitory receptors, signal transduction pathways, and the development of Tregs, that act to eliminate or suppress T cells that recognize self-antigens with too high affinity. This process is essential for maintaining immune homeostasis and preventing autoimmune disease.'
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Proteins (1)

Compounds (30)