CD8-positive, alpha-beta T cell activation

Definition

Target type: biologicalprocess

The change in morphology and behavior of a CD8-positive, alpha-beta T cell resulting from exposure to a mitogen, cytokine, chemokine, cellular ligand, or an antigen for which it is specific. [CL:0000625, GOC:yaf]

CD8-positive, alpha-beta T cell activation is a complex process that involves the recognition of antigen presented by MHC class I molecules on antigen-presenting cells (APCs), leading to a cascade of signaling events that culminate in T cell proliferation, differentiation, and effector function. The process can be broadly divided into three phases: antigen recognition, signaling, and effector function.

**Antigen Recognition:**

1. **MHC-I Presentation:** APCs, such as dendritic cells, macrophages, and B cells, process and present antigen-derived peptides on MHC class I molecules. These peptides are derived from intracellular proteins, including viral proteins, tumor-associated antigens, and self-proteins.
2. **TCR Engagement:** CD8+ T cells express T cell receptors (TCRs) on their surface. These TCRs are highly specific for particular peptide-MHC class I complexes. When a CD8+ T cell encounters an APC displaying its cognate antigen, the TCR binds to the peptide-MHC complex, initiating the activation process.
3. **Costimulatory Signals:** Activation of CD8+ T cells requires not only TCR engagement but also costimulatory signals. These signals are provided by interactions between molecules on the T cell surface, such as CD28, and their ligands on APCs, such as CD80 and CD86. These costimulatory signals ensure that T cells are activated only in the presence of a genuine threat and prevent inappropriate activation.

**Signaling:**

1. **TCR Signaling Cascade:** TCR engagement triggers a cascade of intracellular signaling events. The TCR is associated with a complex of signaling molecules, including CD3, ζ-chain, and the tyrosine kinases Lck and Fyn. Upon TCR engagement, Lck phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) in the CD3 and ζ-chain.
2. **Activation of ZAP-70:** Phosphorylated ITAMs recruit and activate the tyrosine kinase ZAP-70. ZAP-70 then phosphorylates other signaling molecules, including the adaptor protein LAT.
3. **Downstream Signaling:** Phosphorylated LAT serves as a scaffold for the assembly of signaling complexes. These complexes involve various signaling molecules, such as PLCγ1, PI3K, and Ras, which activate downstream pathways, leading to the production of second messengers, such as calcium and diacylglycerol (DAG).

**Effector Function:**

1. **T Cell Proliferation and Differentiation:** The signaling events triggered by TCR engagement lead to the activation of transcription factors, such as NF-κB, NFAT, and AP-1. These transcription factors promote the expression of genes involved in T cell proliferation, survival, and differentiation.
2. **Effector T Cell Development:** Activated CD8+ T cells differentiate into cytotoxic T lymphocytes (CTLs). CTLs are equipped with cytotoxic granules containing perforin and granzyme, which can induce apoptosis in target cells.
3. **Immune Surveillance and Response:** CTLs patrol the body, recognizing and eliminating cells displaying their cognate antigen. This process is essential for the control of viral infections, elimination of tumor cells, and the maintenance of immune homeostasis.

**Note:** CD8-positive, alpha-beta T cell activation is a complex and tightly regulated process. Dysregulation of this process can contribute to autoimmune diseases and cancer. The precise mechanisms of CD8+ T cell activation can vary depending on the specific antigen and APC involved.

This detailed description provides a comprehensive overview of the biological process of CD8-positive, alpha-beta T cell activation, incorporating the various stages, signaling pathways, and effector functions.'"

Proteins (1)

Compounds (8)