Peptide-directed interference of PD-1/PD-L1 binding increases B lymphocyte function after infectious bursal disease viral infection.

Abstract

Programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) binding contributes to immune evasion mechanisms responsible for B lymphocyte exhaustion and apoptosis. This facilitates immunosuppression in chronic viral infections, including infectious bursal disease virus (IBDV). Our previous study showed that PD-1 and PD-L1 expression increases in the peripheral blood mononuclear cells of chickens infected with IBDV. However, due to their high production costs and immune-related adverse events, monoclonal antibodies targeting PD-1 or PD-L1 are unsuitable therapeutic agents. Thus, in the current study, we designed peptides with optimized binding sites for PD-1 and investigated their ability to disrupt PD-1/PD-L1 binding and restore B lymphocyte function in vitro. The peptide gCK-16 exhibited a high affinity for PD-1 (K: 3.37 nM) and effectively inhibited the PD-1/PD-L1 interaction in vitro. Moreover, gCK-16 significantly enhanced B lymphocyte proliferation. Remarkably, gCK-16 treatment abrogated the IBDV-induced upregulation of PD-1/PD-L1, NF-κB activation, and B lymphocyte apoptosis. Additionally, IBDV infection attenuated PI3K/AKT pathway activation in B lymphocytes, while gCK-16 treatment increased immunoglobulin M (IgM) production in IBDV-infected B lymphocytes. Together, these results demonstrate that gCK-16 treatment can potentially enhance B lymphocyte function against IBDV infection, guiding the development of vaccine adjuvants to effectively prevent IBDV-induced avian immunosuppression.