Coestimulatory

Coestimulatory refers to signals that are required, in addition to antigen recognition, for optimal T cell activation, proliferation, and differentiation. These signals are provided by antigen-presenting cells (APCs) and are crucial for a robust and appropriate immune response. Without coestimulatory signals, T cells may become anergic, a state of unresponsiveness, or undergo apoptosis.

The most well-studied coestimulatory pathway involves the interaction between CD28 on the T cell and its ligands, primarily B7-1 (CD80) and B7-2 (CD86), expressed on APCs. Engagement of the T cell receptor (TCR) by peptide-MHC complexes initiates the process of T cell activation. However, for full activation, the CD28 molecule must also bind to B7-1 or B7-2. This dual signal ensures that T cells are activated only when they encounter foreign antigens presented by APCs that are displaying appropriate activation markers.

Other coestimulatory molecules and pathways exist, contributing to the fine-tuning of T cell responses. These include the ICOS/ICOS-L pathway, crucial for T follicular helper cell development, and the CD40/CD40L interaction, important for B cell activation and antibody production. The balance of coestimulatory and coinhibitory signals dictates the outcome of T cell activation, influencing whether an immune response is generated, maintained, or suppressed. Dysregulation of coestimulatory pathways can lead to autoimmune diseases or impaired immune defense.