Two-signal model of t cell activation

Definition

The two-signal model of T cell activation is a framework describing how T cells become activated through two distinct signals. The first signal comes from the recognition of specific antigens presented by antigen-presenting cells (APCs) through major histocompatibility complex (MHC) molecules, while the second signal is a co-stimulatory signal that usually involves interactions between CD28 on T cells and B7 molecules on APCs. This model is crucial for understanding how T cells effectively respond to tumor antigens and participate in immune surveillance against cancer.

5 Must Know Facts For Your Next Test

1. The first signal in the two-signal model occurs when T cell receptors (TCRs) bind to specific antigens presented by MHC molecules on APCs.
2. The second signal is essential for full T cell activation, as it prevents T cells from becoming anergic, or non-responsive, to the antigen.
3. Co-stimulatory molecules such as CD28 and CTLA-4 play pivotal roles in regulating T cell responses during activation.
4. In cancer, effective immune surveillance relies on the ability of T cells to recognize tumor antigens, which is facilitated by the two-signal model.
5. Failure to provide both signals can lead to inadequate T cell responses, allowing tumors to evade immune detection and grow unchecked.

Review Questions

• How do the two signals in T cell activation work together to ensure a robust immune response?
  • The two signals work in tandem to ensure that T cells are not activated without proper context. The first signal involves antigen recognition via MHC molecules, which informs the T cell of a potential threat. The second signal provides necessary co-stimulation that confirms the presence of danger, ensuring that the T cell not only activates but also proliferates and differentiates into effector cells capable of mounting an effective immune response. This two-step process helps prevent inappropriate or excessive immune reactions.
• Discuss the implications of the two-signal model of T cell activation for developing cancer immunotherapies.
  • Understanding the two-signal model has significant implications for cancer immunotherapy strategies. Therapies that enhance co-stimulatory signals can boost T cell responses against tumor antigens, increasing the effectiveness of treatments. For example, immune checkpoint inhibitors target negative regulators like CTLA-4 and PD-1 to enhance T cell activation. By leveraging this model, researchers can design therapies that not only activate T cells but also sustain their responses against tumors, ultimately improving patient outcomes.
• Evaluate how dysregulation of the two-signal model can lead to tumor immune evasion and potential therapeutic targets.
  • Dysregulation of the two-signal model can contribute to tumor immune evasion by either providing insufficient co-stimulation or exploiting immune checkpoints. Tumors may downregulate MHC expression or inhibit co-stimulatory pathways, preventing effective T cell activation and allowing them to escape detection. Therapeutic strategies targeting these dysregulated pathways, such as enhancing co-stimulatory signaling or blocking inhibitory pathways, represent promising approaches to restore anti-tumor immunity and overcome challenges posed by tumors in evading the immune system.

Related terms

Antigen-presenting cells (APCs): Cells that process and present antigens to T cells, primarily including dendritic cells, macrophages, and B cells.

Co-stimulation: A secondary signal required for T cell activation, which enhances the response initiated by antigen recognition.

Tumor antigens: Unique proteins expressed on the surface of tumor cells that can trigger an immune response when recognized by T cells.