B7CD28

B7-CD28 refers to the costimulatory interaction between B7 family ligands on antigen-presenting cells and the CD28 receptor on T cells. The B7 ligands most commonly involved are CD80 (B7-1) and CD86 (B7-2). Engagement of CD28 by these ligands provides a crucial second signal that complements T cell receptor signaling and promotes full T cell activation, proliferation, and survival. The pathway is counterbalanced by CTLA-4, another receptor for B7 ligands, which delivers inhibitory signals to restrain T cell responses.

Mechanistically, T cell activation requires two signals: recognition of antigen-presenting MHC-peptide via the T cell receptor, and costimulation through CD28-B7 binding. CD28 signaling enhances interleukin-2 production, upregulates survival and cell-cycle genes, and supports differentiation of naïve T cells into effector and memory populations. CTLA-4 competes with CD28 for B7 ligands and, having higher affinity, dampens costimulation to limit immune responses. B7 ligand expression on APCs is upregulated upon activation, shaping the magnitude and duration of T cell responses.

Biological role and context, including immunity to infections and cancer, depend partly on B7-CD28 signaling. Proper function supports protective immunity and vaccine responses, while dysregulation can contribute to autoimmunity or inadequate anti-tumor responses. The pathway is also a focal point in therapeutic immunomodulation.

Clinical relevance includes targeted therapies that modulate this axis. Abatacept, a CTLA-4-Ig fusion protein, inhibits B7-CD28 interaction to treat autoimmune diseases by dampening T cell activity. Conversely, CTLA-4 blockade with antibodies such as ipilimumab enhances T cell responses against tumors. Side effects can include increased infection risk and immune-related adverse events.