CD80–Programmed death-ligand 1 interaction (CD80–PD-L1)

The CD80–PD-L1 interaction is a complex protein-protein interaction between the B7 family members CD80 (B7-1) and Programmed death-ligand 1 (PD-L1), serving as a key regulatory node in the immune system [1, 3]. This interaction occurs in two distinct orientations: a cis interaction on the same cell membrane (typically on antigen-presenting cells or tumor cells) and a trans interaction between different cells [2, 12]. The cis interaction is generally immunostimulatory as it sequesters PD-L1, preventing it from engaging the inhibitory PD-1 receptor on T cells, and simultaneously restricts CD80's binding to the inhibitory CTLA-4 receptor while preserving its ability to activate the costimulatory CD28 receptor [1, 5, 15]. In contrast, the trans interaction, such as between a tumor cell and a T cell, is immunosuppressive and can lead to T-cell apoptosis or anergy [2, 8]. Therapeutic agents like the anti-PD-L1 antibodies atezolizumab, durvalumab, and avelumab block this interaction, which can enhance anti-tumor immunity but may also inadvertently affect dendritic cell migration and other homeostatic functions [1, 7, 11]. Consequently, this interaction is a significant target for drug development and a critical factor in the synergy observed in combination immunotherapies [1, 10].

Other names

B7-1–PD-L1 interactionB7-1–B7-H1 interactionCD80–B7-H1 interactioncis-CD80/PD-L1 heterodimer

Disruption of the CD80–PD-L1 protein-protein interaction to modulate T-cell costimulation and coinhibition.