Human CD40
CD40 is a costimulatory receptor essential for immune cell activation and a promising target for cancer immunotherapy and autoimmune disease treatment.
Human CD40
Function
CD40 is a type I transmembrane glycoprotein belonging to the tumor necrosis factor receptor (TNFR) superfamily. It serves as a crucial costimulatory receptor expressed primarily on antigen-presenting cells (APCs) including B cells, dendritic cells, and macrophages. CD40 plays essential roles in adaptive immune responses by facilitating communication between T cells and APCs through its interaction with CD40L (CD154) expressed on activated T cells.Biological Functions
B Cell Activation and Development
- Class Switch Recombination: Essential for immunoglobulin class switching
- Germinal Center Formation: Required for germinal center development and maintenance
- B Cell Survival: Provides survival signals to activated B cells
- Memory B Cell Generation: Important for B cell memory formation
Dendritic Cell Maturation
- DC Activation: Promotes dendritic cell maturation and antigen presentation
- Cytokine Production: Enhances IL-12 production for Th1 differentiation
- Cross-Presentation: Improves cross-presentation of antigens to CD8+ T cells
- Migration: Facilitates DC migration to lymph nodes
Macrophage Activation
- M1 Polarization: Promotes pro-inflammatory macrophage activation
- Antimicrobial Activity: Enhances killing of intracellular pathogens
- Antigen Presentation: Improves macrophage antigen presentation capacity
- Tissue Repair: Involved in wound healing and tissue remodeling
Target Details
Protein Information
Protein Information
Organism: Homo sapiens (Human)
Gene Name: CD40
Alternative Names: TNFRSF5, Bp50
Protein Family: TNF receptor superfamily
Database References
Database References
UniProt ID: P25942
Gene ID: 958
NCBI Reference: P25942-1
Protein Region: Glu 21 - Arg 193 (extracellular domain)
Structural Information
Structural Information
Molecular Weight: ~48 kDa (full-length), ~20 kDa (extracellular domain)
Structure: Four cysteine-rich domains (CRDs) typical of TNFR family
Key Features: Signal peptide, CRDs, transmembrane domain, cytoplasmic tail
Binding Partner: CD40L (CD154) on T cells
Signaling Pathways
Signaling Pathways
Primary Pathway: NF-κB activation via TRAF proteins
Secondary Pathways: MAPK, PI3K/Akt, p38
Downstream Effects: Gene transcription, cell survival, activation
Regulation: TRAF proteins, SOCS proteins, negative feedback loops
Therapeutic Applications
Cancer Immunotherapy
CD40 agonism represents a promising approach for cancer treatment:Mechanism of Action
- DC Activation: Enhances tumor antigen presentation
- T Cell Priming: Improves anti-tumor T cell responses
- Macrophage Repolarization: Converts tumor-associated macrophages to anti-tumor phenotype
- Tumor Microenvironment: Modifies immunosuppressive tumor environment
Clinical Development
- Agonistic Antibodies: CP-870,893, dacetuzumab, lucatumumab
- CD40L Mimetics: Small molecules and peptides mimicking CD40L
- Combination Therapies: CD40 agonists with checkpoint inhibitors, chemotherapy
- Solid Tumors: Pancreatic cancer, melanoma, lymphoma
Autoimmune Diseases
CD40 blockade is being explored for autoimmune conditions:- Rheumatoid Arthritis: Blocking aberrant B cell and macrophage activation
- Systemic Lupus Erythematosus: Reducing autoantibody production
- Multiple Sclerosis: Modulating CNS inflammation
- Transplant Rejection: Preventing graft rejection
Research Applications
Vaccine Development
- Adjuvant Effects: CD40 agonists as vaccine adjuvants
- Enhanced Immunity: Improving vaccine-induced immune responses
- Mucosal Immunity: Enhancing mucosal vaccine efficacy
- Cancer Vaccines: Therapeutic cancer vaccine development
Immunological Research
- B Cell Biology: Understanding B cell activation and differentiation
- T Cell-APC Interactions: Studying immune synapse formation
- Germinal Center Biology: Investigating antibody affinity maturation
- Tolerance Mechanisms: Understanding peripheral tolerance breakdown
Drug Discovery
- Agonist Development: Small molecule and biological CD40 agonists
- Antagonist Screening: Inhibitors for autoimmune disease treatment
- Bispecific Antibodies: CD40-targeted combination therapies
- Delivery Systems: Targeted drug delivery via CD40
Clinical Considerations
CD40 Agonist Therapy
Potential Benefits
- Enhanced Anti-Tumor Immunity: Improved T cell and NK cell responses
- Durable Responses: Potential for immunological memory
- Combination Potential: Synergy with other immunotherapies
- Biomarker-Guided: Predictive biomarkers for response
Safety Concerns
- Cytokine Release Syndrome: Systemic inflammatory responses
- Autoimmunity: Risk of autoimmune reactions
- Hepatotoxicity: Liver inflammation and damage
- Dosing Challenges: Narrow therapeutic window
CD40 Antagonist Therapy
Applications
- Autoimmune Diseases: Blocking pathogenic immune responses
- Transplantation: Preventing graft rejection
- Allergic Diseases: Reducing allergic inflammation
- Inflammatory Conditions: Treating chronic inflammatory diseases
Considerations
- Immunosuppression: Risk of infections and malignancies
- B Cell Function: Impaired humoral immunity
- Vaccine Responses: Reduced vaccine efficacy
- Long-term Effects: Unknown consequences of chronic CD40 blockade
Biomarker Applications
Disease Monitoring
- Soluble CD40: Serum levels correlate with disease activity
- CD40 Expression: Tissue expression patterns in various diseases
- Signaling Activity: Downstream pathway activation
- Response Prediction: Biomarkers for therapy response
Research Tools
- Flow Cytometry: CD40 expression analysis
- Functional Assays: CD40 signaling pathway studies
- Imaging: CD40 distribution in tissues
- Proteomics: CD40 interactome analysis
CD40 is available in our target library as both membrane-bound and soluble forms. The extracellular domain construct (Glu 21 - Arg 193) is most commonly used for binding studies and therapeutic development. We also offer CD40L for studying the CD40-CD40L interaction.
CD40 represents both an agonist target (for cancer immunotherapy) and an antagonist target (for autoimmune diseases). When designing binding studies, consider whether you’re developing agonistic or antagonistic molecules, as this will influence your experimental design and interpretation of results.