PD-L2 suppresses B-1 cell antibody production against phosphorylcholine (PC), a self-antigen. PD-L2-deficient mice exhibit elevated PC-specific IgM and plasmablasts, correlating with increased IL-5 production, a key B-1 cell differentiation factor . Conversely, PD-L2 blockade enhances B-1 cell activation, suggesting therapeutic potential in autoimmune diseases or infections.
PD-L2 is an emerging biomarker for immune checkpoint inhibitor (ICI) therapy. A radiolabeled PD-L2 antibody (124/125I-ATL2) demonstrated high specificity in detecting PD-L2 expression in lung cancer models:
Tumor Uptake: 7.11 ± 0.38 %ID/g in PD-L2-expressing A549-PDL2 tumors vs. 2.72 ± 0.15 %ID/g in non-expressing controls .
PET/CT Imaging: Significant tumor signal 24 hours post-injection, confirming non-invasive PD-L2 quantification .
PD-L2-specific T cells recognize epitopes like PD-L205 (aa 16–25) and PD-L201 (aa 4–12), with responses observed in both healthy donors and cancer patients. These T cells specifically target PD-L2-expressing dendritic cells, suggesting PD-L2 vaccination strategies for hematologic malignancies .
Antibody Validation: Rigorous characterization (e.g., Western Blot, IHC) is critical to avoid cross-reactivity, as highlighted by initiatives like NeuroMab and the Antibody Characterization Laboratory .
Therapeutic Targets: PD-L2’s role in immune suppression and tumor evasion positions it as a candidate for combination therapies with anti-PD-1/PD-L1 agents.
Diagnostic Utility: Radiolabeled PD-L2 antibodies (e.g., 124I-ATL2) may enable personalized treatment selection by identifying PD-L2-expressing tumors .