Abatacept is a fusion protein that inhibits T cell activation by blocking interaction between which molecules?

• A. CD40 on B cells and CD40L on T cells
• B. CD28 on T cells and CD80/CD86 on APCs
• C. CD3 on T cells and ZAP-70
• D. MHC and TCR

Answer: (B)

T cell activation requires a second, costimulatory signal in addition to the TCR recognizing antigen-MHC. This second signal comes from CD28 on T cells binding to CD80/CD86 on antigen-presenting cells. Abatacept is a CTLA-4–Ig fusion protein that binds CD80/CD86 with high affinity, effectively blocking this costimulatory interaction. Without the CD28–CD80/CD86 signal, T cells don’t fully activate, leading to reduced IL-2 production and T cell proliferation, which helps dampen autoimmune inflammation. The other interactions described—MHC with TCR (antigen recognition), CD3 with ZAP-70 (proximal TCR signaling), and CD40–CD40L (B cell co-stimulation)—are not what abatacept targets.