CD4⁺ T cells are activated through interaction with antigen-MHC Class II complexes presented by antigen-presenting cells (APCs).
Here's a more detailed breakdown:
The Activation Process
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Antigen Presentation: APCs, such as dendritic cells, macrophages, and B cells, engulf and process antigens (e.g., from pathogens). They then display fragments of these antigens bound to MHC Class II molecules on their cell surface.
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T Cell Receptor (TCR) Interaction: Naive CD4⁺ T cells circulate through the body, surveying APCs. When a CD4⁺ T cell encounters an APC displaying an antigen-MHC Class II complex that its TCR specifically recognizes, it initiates an interaction. The TCR binds to the antigen-MHC Class II complex.
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Co-stimulatory Signals: TCR binding alone is not sufficient for full T cell activation. Co-stimulatory molecules on the APC surface, such as B7 (CD80 or CD86), must bind to their receptor, CD28, on the T cell. This provides a second signal crucial for activation and preventing anergy (T cell unresponsiveness).
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Cytokine Milieu: The specific cytokines present in the microenvironment during T cell activation influence the differentiation of the CD4⁺ T cell into different subtypes (e.g., Th1, Th2, Th17, Treg). For example, IL-12 promotes Th1 differentiation, while IL-4 promotes Th2 differentiation.
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T Cell Proliferation and Differentiation: Once activated, the CD4⁺ T cell undergoes clonal expansion, rapidly dividing to produce a large population of cells with the same antigen specificity. It also differentiates into effector cells, which perform specific functions to help eliminate the antigen. Effector functions include:
- Helping B cells produce antibodies: Th2 cells are particularly important for this.
- Activating macrophages to kill intracellular pathogens: Th1 cells are key for this.
- Recruiting and activating other immune cells: Th17 cells play a role in this, especially against extracellular bacteria and fungi.
- Suppressing immune responses: Treg cells help maintain immune homeostasis and prevent autoimmunity.
Summary
Activation of CD4⁺ T cells is a complex process that requires a specific TCR-antigen/MHC Class II interaction, co-stimulatory signals, and a supportive cytokine environment. This activation leads to proliferation and differentiation into various effector subtypes that orchestrate adaptive immune responses.
