Question

Describe co-stimulatory pathway for T-cell activation.

Hint:

Co-stimulatory signals are essential for T-cell activation, and disruptions in these pathways can lead to immune dysfunction, including autoimmunity or immunodeficiency.

Answer 1

Step 1: Overview of T-Cell Activation:
T-cell activation is a critical process in immune responses. The activation requires two signals: the primary signal is provided by the T-cell receptor (TCR) interacting with the peptide-MHC complex on antigen-presenting cells (APCs), and the secondary signal is provided by co-stimulatory molecules. Without the co-stimulatory signal, T-cell activation is incomplete, and the T-cell may undergo anergy or apoptosis.
Step 2: Co-Stimulatory Pathway for T-Cell Activation:
The key co-stimulatory pathways include: 1. CD28 and B7 Interaction: The interaction between CD28 (on T-cells) and B7 molecules (on APCs) is the primary co-stimulatory signal. This binding results in the full activation of T-cells and promotes cytokine production.
2. ICOS and ICOS-L Interaction: Inducible T-cell co-stimulator (ICOS) on activated T-cells interacts with ICOS ligand (ICOS-L) on APCs. This pathway plays a critical role in the differentiation of T-helper cells and the maintenance of immune responses.
3. CD40 and CD40L Interaction: The interaction between CD40 (on APCs) and CD40 ligand (CD40L) (on T-cells) is important in the activation of APCs and in promoting the T-helper cell response.
4. CD137 (4-1BB) and CD137L Interaction: CD137 (a member of the TNF receptor family) interacts with CD137L on APCs, enhancing T-cell proliferation and cytokine production.
Step 3: Regulatory Co-Stimulatory Pathways:
In addition to positive co-stimulatory signals, there are negative co-stimulatory pathways that regulate T-cell responses: 1. CTLA-4 and B7 Interaction: CTLA-4 (Cytotoxic T-Lymphocyte Antigen-4) competes with CD28 for binding to B7, delivering an inhibitory signal that limits T-cell activation.
2. PD-1 and PD-L1/PD-L2 Interaction: The interaction of PD-1 (Programmed Cell Death Protein 1) with its ligands (PD-L1/PD-L2) on APCs and tumor cells leads to T-cell exhaustion, a mechanism to prevent autoimmunity.