What signals are required for T-cell activation?

T-cell activation requires three distinct signals delivered in sequence. 

Signal One: Antigen Recognition

T-cell receptors (TCRs) on the surface of a T cell recognize and bind to a specific antigen. The initial T-cell activation is triggered when the TCR on the surface of a T cell recognizes their complementary antigen that is presented by Major Histocompatibility Complex (MHC) molecules on the surface of antigen presenting cells (APCs). This binding occurs in the secondary lymphoid organs and sets in motion the subsequent response. 

Signal Two: Co-stimulation and Expansion

Although T-cell activation is triggered when the TCR binds to the antigen-loaded MHC, T-cells require a number of secondary or co-stimulatory signals to become fully activated and respond effectively to the threat. These co-stimulatory signals are provided by CD28, a molecule present on T cells. CD28 interacts with one of two B7 molecules on the APC, initiating the clonal expansion of T cells, which results in the production of millions of T cell clones that recognize the same antigen. 

Signal Three: Cytokine-Mediated Differentiation 

Cytokines, which are signaling molecules, send instructions to the T cells and determine which type of responder the cell will become. Once the cell has received its instructions it performs a specific task in the tissue and also influences further immune responses. 

The newly formed army of T cells, each with their well-defined tasks, move out to the site of infection or inflammation in order to fight off the pathogen.