Butyrophilin and Butyrophilin-like Proteins: B7-related Modulators of T Cell Function
 
Timothy Manning, Jinghua Wang, Brian Manick, Guoping Wu, Vassili Kalabokis
R&D Systems Inc, Bio-Techne Corp. Minneapolis, MN 55413
 
Butyrophilin (BTN) and BTN-like proteins have a homologous structure to the widely-studied B7 family of immuno-modulatory receptors. BTNs are receiving increased attention for potential roles in immunotherapy, and may represent a novel subset of immune checkpoint regulators. In this study, we expressed and purified the extracellular domain of recombinant human BTNs and BTN-like proteins, and investigated their biological functions in vitro. Human or mouse CD3⁺ T cells were treated with plate-bound anti-CD3 antibody and BTN or BTN-like proteins. The levels of IL-2 were measured in cell culture supernatants using R&D Systems® Quantikine® ELISA kit. BTNL3 and BTNL9 markedly inhibited anti-CD3-induced IL-2 in a dose dependent manner. In contrast, BTN3A2 and BTNL8 significantly increased T-cell derived IL-2. Taken together, our data suggests that BTNL3 and BTNL9 act as T cell co-inhibitory molecules, while BTN3A2 and BTNL8 are co-stimulatory molecules that enhance T cell activation. The T cell receptor mediating these effects has yet to be identified. The results highlight the potential that BTN and BTN-like proteins may be novel therapeutic targets of immune checkpoint pathways.