Three signals before a naive T cell commits
A naive T cell does not act on a single cue. Full activation generally requires three signals. Signal one is recognition: the T cell receptor (TCR) binds a specific peptide displayed on an MHC molecule of an antigen-presenting cell. Signal two is costimulation, classically the CD28 molecule on the T cell engaging B7 proteins (CD80/CD86) on the presenting cell.
Signal three is the cytokine environment, which shapes how the activated cell differentiates. Requiring more than recognition alone is a safeguard against attacking the body's own tissue.
Why missing costimulation causes tolerance
If a T cell receives signal one without signal two, it does not simply pause; it can be switched into an unresponsive state called anergy or be deleted. This helps enforce tolerance to self, because antigen-presenting cells generally only display costimulation when they have detected genuine danger.
This logic is exploited in medicine: some drugs block costimulation to dampen unwanted immune activation, and checkpoint pathways that normally restrain T cells are targeted in cancer therapy. This is general educational information about immunology, not medical advice.