Recombinant Mouse Poliovirus receptor-related protein 2 (Pvrl2)

Protein Domains

• Extracellular region: Gln32–Gly351, containing three immunoglobulin (Ig)-like domains:

  • One N-terminal variable (V)-type Ig domain (mediates ligand binding)

  • Two constant (C2)-type Ig-like domains (support structural stability)

• C-terminal 6-His tag: Facilitates purification and detection

Cell Adhesion and Immune Regulation

• Homophilic binding: Mediates intercellular adhesion via trans-homodimerization at cell–cell junctions .

• Heterophilic interactions: Binds DNAM-1 (CD226) on NK and T cells to stimulate cytotoxicity, while engagement with PVRIG (CD112R) or TIGIT suppresses immune activation .

Role in Cancer Immunology

• Tumor expression: Overexpressed in breast, ovarian, endometrial, and prostate cancers, correlating with immunosuppression .

• Immune checkpoint axis:

  • PVRL2–PVRIG: Dominant inhibitory pathway suppressing NK/T-cell activity .

  • PVRL2–DNAM-1: Weak co-stimulatory signal overshadowed by PVRIG binding .

Experimental Use Cases

• Cell adhesion assays: Studying junction formation in epithelial/endothelial models .

• Immune cell modulation: Assessing NK/T-cell activation or inhibition in co-culture systems .

• Therapeutic targeting: Evaluating anti-PVRIG antibodies in preclinical cancer models .

Advantages of Carrier-Free (CF) Recombinant Protein

• BSA-free formulation: Eliminates interference in ligand-binding assays or in vivo studies .

• Stability: Stable for ≥6 months at -20°C (avoid repeated freeze-thaw cycles) .

Immune Checkpoint Blockade

• PVRIG inhibitors: Enhance NK-mediated killing of PVRL2+ tumors (e.g., AML, ovarian cancer) .

• Combination therapies: Synergy observed with PD-1/PD-L1 blockade in murine models .

Expression Correlations

• Poor prognosis: High PVRL2 levels in tumors associate with T-cell exhaustion markers (PD-1, TIM-3) .

• Soluble PVRL2: Detected in serum of cancer patients; potential biomarker under investigation .

Key Research Findings

1. Murine studies: PVRIG deletion enhances CD8+ T-cell effector function and synergizes with anti-PD-L1 to reduce tumor growth .

2. Structural insights: The V-type Ig domain is critical for herpesvirus entry (e.g., HSV-2), though Pvrl2 does not bind poliovirus .

3. Adhesion dynamics: Localizes to cell–cell contact sites in neuroblastoma cells, stabilizing adherens junctions .

Future Directions

• Isoform-specific studies: Functional differences between Nectin-2α and Nectin-2δ remain underexplored.

• Clinical trials: Phase I/II trials targeting PVRL2–PVRIG in gynecologic cancers (NCT03667716, NCT04370704) .