Activation of CD8+ T Cells

What is required for the activation of CD8+ T cells?

What is required for the differentiation of naive CD8+ T cells into fully active cytotoxic T lymphocytes (CTLs) and memory cells?

What happens within minutes of antigen recognition in activated T cells?

Which of the following is not a consequence of signal transduction pathways emanating from the TCR complex and costimulatory receptors?

Which of the following is not one of the biochemical pathways of T cell activation described in the text?

What is the main difference between the response pathways of CD4+ and CD8+ T lymphocytes described in the text?

What is the primary function of CTLA-4 in T cell activation?

Which of the following is the correct order of events in the NFAT pathway?

What is the primary role of the Ras/Rac-MAP kinase pathways in T cell activation?

Which of the following molecules is directly involved in the initiation of the NFAT pathway?

What is the primary role of the CD3 and ζ chains in T cell activation?

What is the primary function of the enzyme calcineurin in the NFAT pathway?

Stimuli for Activation of CD8+ T Cells

Recognition of class I MHC-associated peptides stimulates CD8+ T cell activation
Costimulation and helper T cells are required for activation
Naive CD8+ T cells differentiate into cytotoxic T lymphocytes (CTLs) and memory cells with help from CD4+ helper T cells

Biochemical Pathways of T Cell Activation

Antigen recognition triggers new gene transcription and protein synthesis in T cells within minutes
Signal transduction pathways from the TCR complex and costimulatory receptors lead to protein expression
Expressed proteins mediate T-cell proliferation, differentiation, and effector functions

Initial Responses of Activated T Cells

c-Fos transcription factor is produced, initiating protein production
IL-12 cytokine promotes T cell survival and proliferation
Cell division is initiated
CD69 expression is involved in cell migration
IL-2R expression allows reception of IL-2 cytokine
CD40 ligand is an effector molecule of T cells
CTLA-4 is expressed for regulation if needed

Signal Transduction Pathways

Antigen recognition activates enzymes, recruits adaptor proteins, and produces functional transcription factors
Binding of MHC of APC to TCR initiates signaling
Signals from the TCR complex are transmitted via Lck of the CD4/CD8 receptor
CD3 and ζ chains contain ITAMs, sending signals to the T cell body via ZAP-70

Downstream Biochemical Pathways

TCR complex signal transduction leads to multiple biochemical pathways, including:
- Nuclear factor of activated T cells (NFAT) pathway
- Ras/Rac-MAP kinase pathways (AP-1)
- Protein kinase C (NF-κB) pathway
- Lipid kinase pathways (various proteins)

NFAT Pathway

NFAT transcription factor is present in an inactive phosphorylated form in the cytosol
Phospholipase Cγ (PLCγ) is activated, leading to:
- Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-triphosphate (IP3)
- Release of calcium ions in the cytosol, activating calcineurin phosphatase
- De-phosphorylation of NFAT, allowing it to migrate to the nucleus and activate gene promoters, including IL-2 and components of IL-2 receptors

Learn about the stimuli for activation of CD8+ T cells, including recognition of class I MHC–associated peptides, costimulation, and activation pathways. Understand the differentiation of naive CD8+ T cells into cytotoxic T lymphocytes (CTLs) and memory cells.