An antigen-presenting cell (APC) will neither activate nor inactivate a T cell if the appropriate antigen is not present on the APC surface, even if it expresses a co-stimulatory molecule and can deliver signal 2 (left panel). However, when a T cell recognizes antigen in the absence of co-stimulatory molecules, it receives signal 1 alone and is inactivated (right panel). This allows self antigens expressed on tissue cells to induce tolerance in the peripheral T-cell population.