Which interaction provides the second signal for T cell activation?

• A. TLR binds MHC II
• B. B7 on APC binds CD28 on T cell
• C. CD40 on B cell binds CD40L
• D. CD28 binds MHC I

Answer: (B)

T cell activation requires two signals. The first comes from the T cell receptor recognizing peptide antigen presented by MHC on an antigen-presenting cell. The second signal is provided by a costimulatory interaction between B7 molecules on the APC and CD28 on the T cell. This costimulation is essential for full activation, IL-2 production, and clonal expansion; without it, the T cell can become anergic or die despite recognizing antigen. Other interactions don’t deliver this direct second signal: TLR binding to MHC II is innate sensing that upregulates costimulators but doesn’t directly activate the T cell; CD40-CD40L supports B cell help and APC activation rather than being the direct second signal for naive T cells; and CD28 does not bind MHC I—CD28 binds B7.