positive regulation of CD8-positive, alpha-beta T cell activation

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of CD8-positive, alpha-beta T cell activation. [GOC:obol]

Positive regulation of CD8-positive, alpha-beta T cell activation is a complex biological process that involves a cascade of signaling events initiated by the interaction of the T cell receptor (TCR) with its cognate antigen presented on the surface of antigen-presenting cells (APCs). The TCR, a heterodimer composed of alpha and beta chains, recognizes specific peptide antigens presented in the context of major histocompatibility complex (MHC) class I molecules on APCs.

Upon TCR engagement, a series of intracellular signaling pathways are activated, leading to the activation and proliferation of CD8-positive, alpha-beta T cells. These pathways include:

1. **The ITAM-mediated signaling pathway:** The TCR complex is associated with signaling molecules called CD3 proteins, which contain immunoreceptor tyrosine-based activation motifs (ITAMs). Upon TCR engagement, tyrosine kinases such as Lck and Fyn phosphorylate the ITAMs on CD3 proteins. This phosphorylation event creates docking sites for the recruitment and activation of the tyrosine kinase ZAP-70.
2. **ZAP-70 activation and downstream signaling:** Activated ZAP-70 phosphorylates downstream signaling molecules, including LAT (linker for activation of T cells) and SLP-76 (SH2 domain-containing leukocyte protein of 76 kDa). These phosphorylated molecules serve as scaffolds for the assembly of signaling complexes that activate multiple downstream pathways.
3. **Activation of the MAPK pathway:** One of the key downstream pathways activated by ZAP-70 is the mitogen-activated protein kinase (MAPK) pathway. This pathway leads to the activation of transcription factors, such as AP-1 and NF-κB, which regulate the expression of genes involved in T cell activation and proliferation.
4. **Activation of the PI3K-Akt pathway:** Another important pathway activated by ZAP-70 is the phosphoinositide 3-kinase (PI3K)-Akt pathway. This pathway regulates cell survival, metabolism, and proliferation.
5. **Calcium signaling and NFAT activation:** Activation of the TCR also leads to the influx of calcium ions into the T cell. This calcium influx activates the transcription factor NFAT (nuclear factor of activated T cells), which plays a crucial role in regulating gene expression during T cell activation.

The activation of these signaling pathways leads to the expression of a wide range of genes, including those encoding cytokines, chemokines, and other effector molecules. These molecules contribute to the development of a robust immune response against pathogens and other threats.

Moreover, the process of positive regulation of CD8-positive, alpha-beta T cell activation is tightly regulated by a complex network of inhibitory receptors and signaling pathways. These negative regulatory mechanisms ensure that the immune response is appropriately controlled and does not cause excessive inflammation or autoimmune damage.

In summary, positive regulation of CD8-positive, alpha-beta T cell activation is a highly orchestrated process involving multiple signaling pathways and transcription factors. The precise coordination of these events ensures the appropriate activation of CD8-positive, alpha-beta T cells, which are critical for mounting an effective immune response against pathogens and tumors.'
"

Proteins (1)

Compounds (8)