T-lymphocyte activation antigen CD80 and Programmed cell death 1 ligand 1 interaction interface (CD80:PD-L1 interface)

The B7.1 (CD80) and PD-L1 (CD274) interaction interface is a critical regulatory site where two key immune checkpoint proteins bind to one another, primarily in a cis orientation on the same cell membrane (Sugiura et al., 2019, Science). This interaction is distinct from the well-characterized B7.1/CD28 costimulatory pathway and the PD-L1/PD-1 inhibitory pathway. When B7.1 and PD-L1 are bound at this interface, B7.1 is sequestered and unable to bind to CD28, while PD-L1 is similarly restricted from binding to PD-1 (Chaudhri et al., 2018, Journal of Biological Chemistry). In the tumor microenvironment, high expression of PD-L1 can lead to the masking of B7.1, thereby depriving T-cells of necessary costimulatory signals and promoting immune evasion (Butt et al., 2014, Immunity). Therapeutic monoclonal antibodies such as Atezolizumab are designed to bind PD-L1 in a manner that disrupts both its interaction with PD-1 and its interaction with B7.1, effectively liberating B7.1 to enhance T-cell activation (Herbst et al., 2014, Nature). Understanding this interface is crucial for optimizing checkpoint inhibitor therapies and overcoming resistance in various malignancies.

Other names

B7.1:PD-L1 interfaceCD80:CD274 interactionB7-1:B7-H1 complexCis-B7.1/PD-L1 interactionB7-1:PD-L1 heterodimer

Disruption of the physical interaction between CD80 and PD-L1 to prevent the sequestration of CD80, thereby restoring its availability for CD28-mediated costimulation while simultaneously blocking PD-L1/PD-1 inhibitory signaling.