What co-stimulatory signal is required for full T cell activation, and what happens if it is absent?

• A. CD40 on T cells binds CD28 on B cells; without it, T cells fail to activate.
• B. CTLA-4 on T cells binds B7 to promote activation.
• C. PD-1 on T cells binds PD-L1; blocking it enhances activation.
• D. CD28 on T cells binds B7 (CD80/86) on antigen-presenting cells; without it, T cells become anergic.

Answer: (D)

T cell activation needs two signals: the first is the T cell receptor recognizing antigen presented by an antigen-presenting cell, and the second is a co-stimulatory signal that confirms the response is appropriate. The key co-stimulatory interaction is CD28 on the T cell binding to B7 (CD80/CD86) on the antigen-presenting cell. This second signal drives the T cell to produce IL-2, proliferate, and differentiate into an effective effector cell.

If this co-stimulatory signal is absent, the T cell does not fully activate in response to antigen alone and becomes anergic, entering a state of hyporesponsiveness where it cannot respond even if later encounters the antigen with signal one. This mechanism helps prevent accidental or excessive immune activation.

Inhibitory pathways like CTLA-4 binding B7 and PD-1 binding PD-L1 actually dampen activation, not promote it, and are not the required costimulatory signal. The interaction involving CD40 and CD28 is not the primary T cell co-stimulatory signal.