Which interaction provides the co-stimulatory signal necessary for naive T cell activation?

• A. B7 with CD28
• B. MHC with TCR
• C. CD40 with CD40L
• D. IL-2 receptor activation

Answer: (A)

Naive T cell activation hinges on two signals. The first is the T cell receptor recognizing a peptide-MHC complex, which provides specificity. But without a second, co-stimulatory cue, the T cell may become anergic. The classic co-stimulatory interaction is the B7 molecules (CD80/CD86) on the antigen-presenting cell engaging CD28 on the naive T cell. This signal 2 is what fully activates the T cell, promoting IL-2 production and clonal expansion.

So, the B7-CD28 interaction is the key co-stimulatory step that enables naive T cells to respond effectively. The MHC-TCR engagement supplies the antigen-specific trigger but does not by itself provide the necessary co-stimulation. CD40-CD40L is important for licensing APCs and helping B cells, and IL-2 receptor signaling drives proliferation after activation, but neither is the direct initial co-stimulatory signal for a naive T cell.