CD4 Antibody
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Description
Structure and Function of CD4 Antibodies
CD4 antibodies are engineered to bind specifically to the CD4 glycoprotein, which functions as a co-receptor for the T-cell receptor (TCR) and facilitates interactions with MHC class II molecules on antigen-presenting cells. The CD4 protein comprises four immunoglobulin-like domains (D1-D4) and interacts with the β2-domain of MHC II via its D1 domain .
Types of CD4 Antibodies:
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Immunoadhesins: Fusion proteins combining CD4 with immunoglobulin Fc domains (e.g., CD4-IgG1). These enhance plasma half-life and effector functions like antibody-dependent cell-mediated cytotoxicity (ADCC) .
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Monoclonal Antibodies: Target-specific epitopes on CD4, such as MAX.16H5 (blocks CD4 interactions with MHC II) or 13B8.2 (antagonizes HIV gp120 binding) .
Clinical Applications
CD4 antibodies have been explored in:
a. HIV/AIDS Therapy
CD4 immunoadhesins mimic natural CD4 to bind HIV’s gp120 envelope protein, preventing viral entry into host cells. Preclinical studies demonstrate efficacy in blocking infection and inducing cytokine production (e.g., IL-2, IFN-γ) .
b. Autoimmune Diseases
MAX.16H5 shows promise in treating rheumatoid arthritis and lupus by modulating T-cell responses. Phase I/II trials highlight reduced immune activation and antigen-specific tolerance .
c. Graft-Versus-Host Disease (GVHD)
Ex vivo treatment of allogeneic hematopoietic stem cell transplants with MAX.16H5 suppresses GVHD while preserving graft-versus-leukemia (GVL) effects, improving survival rates .
Mechanism of Action
CD4 antibodies act through:
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Direct Blocking: Preventing CD4 interactions with MHC II or viral proteins (e.g., gp120) .
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Immunomodulation: Inducing tolerance by disrupting T-cell activation signals .
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ADCC Activation: Recruiting immune effector cells to eliminate infected or autoreactive cells .
Research Findings
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HIV Studies: CD4-IgG1 fusion proteins exhibit 10-fold higher binding affinity to gp120 compared to soluble CD4 .
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Autoimmune Models: MAX.16H5 reduces immune responses to tetanus toxoid by 70% in murine models .
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GVHD Trials: Allogeneic transplants treated with MAX.16H5 achieve 90% survival in preclinical leukemia models .
Challenges and Future Directions
Product Specs
Buffer
PBS with 0.02% Sodium Azide, 50% Glycerol, pH 7.3. Store at -20°C. Avoid freeze/thaw cycles.
Lead Time
Typically, we can ship your orders within 1-3 business days of receipt. Delivery times may vary depending on the purchase method or location. Please consult your local distributors for specific delivery information.
Synonyms
CD4; T-cell surface glycoprotein CD4; T-cell surface antigen T4/Leu-3; CD antigen CD4
Target Names
Uniprot No.
Target Background
Function
CD4 is an integral membrane glycoprotein that plays a critical role in the immune response. It serves multiple functions in defending against both external and internal threats. Within T-cells, CD4 primarily acts as a coreceptor for the MHC class II molecule:peptide complex. Antigens presented by class II peptides originate from extracellular proteins, while class I peptides are derived from cytosolic proteins. CD4 interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen-presenting cells (APCs). This interaction recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates various intracellular signaling pathways by phosphorylating different substrates, ultimately leading to lymphokine production, motility, adhesion, and activation of T-helper cells. In other cells, such as macrophages or NK cells, CD4 participates in differentiation/activation, cytokine expression, and cell migration through a TCR/LCK-independent pathway. It contributes to the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages. Additionally, CD4 serves as the primary receptor for human immunodeficiency virus-1 (HIV-1) and is down-regulated by HIV-1 Vpu. It also functions as a receptor for Human Herpes virus 7/HHV-7.
Gene References Into Functions
- CD4 receptor levels are significantly reduced in THP-1 differentiated cells. This down-regulation of the viral receptor is attributed to the up-regulation of miR-221/miR-222 during differentiation. Notably, in a THP-1 cell line stably expressing a modified CD4 that is not modulated by miR-221/miR-222, productive HIV-1 infection occurs after cell differentiation. PMID: 29301198
- Human BD-2 and BD-3 play a positive and negative regulatory role in the development and proliferation of human effector CD4+ T cells. This regulation is essential for optimal adaptive immune responses and the control of immunopathology. PMID: 30098283
- Research highlights regions of cross-talk between gp120 and gp41 and identifies residues within the heptad repeat region 1 (HR1) that play crucial roles in regulating CD4-induced conformational changes in Env. PMID: 29875245
- Peripheral lymphocytes, specifically CD4(+) and CD19(+), from patients in the early stages of Alzheimer's disease exhibit mitochondrial depletion, as observed at both the DNA and protein levels. PMID: 28923392
- Human microRNAs-221 and -222 inhibit HIV-1 entry into macrophages by targeting the CD4 viral receptor. PMID: 28978468
- CD4 possesses four ecto-domains (D1-D4), with D1, D2, and D4 each containing a unique disulfide bond. Reduction of the D2 disulfide bond decreases the dynamics of its surrounding beta-strands. A favorable inward collapse of structure occurs around the D2 disulfide after reduction. PMID: 29470989
- Findings suggest that CD4 expression and older age are adverse prognostic factors in wild-type NPM1, FLT3-ITD-negative CN-AML. PMID: 28318150
- Studies investigated the prevalence, magnitude, and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8(+) and CD4(+) T-cell responses against MAGE-A family antigens were detected in 44% (20/45) of patient samples assayed by ex vivo IFN-gamma ELISPOT. This suggests that spontaneous T-cell immunity against CTAg proteins develops in many patients with testicular cancer. PMID: 28555838
- Depletion of the gamma2 or mu1A (AP1M1) subunits of AP-1, but not of gamma1 (AP1G1), prevents Nef-mediated lysosomal degradation of CD4. PMID: 27909244
- Research provides a mechanistic explanation for previous observations that dimerization-defective Nef mutants fail to down-regulate CD4, validating the Nef dimerization interface as a potential target for antiretroviral drug development. PMID: 28031466
- Mouse leukemia cell lines capable of expressing hCD4 and CCR5 were established to facilitate normal entry of HIV-1. This allows the use of a human CD4/CCR5 transgenic mice cell model for investigating the transmission and pathogenesis of HIV/AIDS and potential antiviral drugs against this disease. PMID: 28028680
- The percentage of lamina propria CD4+LAP+ cells is elevated in active ulcerative colitis, indicating reduced suppressor activity due to their increased proportion of intracellular IL-17 expression. PMID: 26589955
- DNA microarray analysis identified potential therapeutic targets for childhood severe asthmatics. PMID: 25979195
- The study provides insights into the role of CD4 on cell membrane mechanical characteristics. PMID: 26362701
- A decrease in CD4(+) CD25(+) CD127(low) FoxP3(+) regulatory T cells with impaired suppressive function has been observed in untreated ulcerative colitis patients. PMID: 26333292
- Redox shuffling of the allosteric disulfide results in previously undescribed conformational changes in CD4. These changes are likely essential for its interaction with its protein partners. PMID: 27009680
- Elevated levels of activated and highly susceptible HIV-1 target cells, reduced CD4, enhanced CXCR4 cell surface expression, coupled with the high susceptibility to FAS-induced programmed cell death, may contribute to the rapid CD4+ T cell depletion. PMID: 26452480
- HRB knock-down affected CD4 downregulation induced by Nef but not by HIV-1 Vpu. PMID: 26701340
- Increased CD4, IL-17, and COX-2 expression are associated with subclinical inflammation in malar melasma. PMID: 26381025
- CD4 receptor induced HIV size expansion prior to cell entry. PMID: 26432024
- Sustained expression of CD83 was observed when CD4+ T cells were induced by transforming growth factor-beta to differentiate into CD4+CD25+ forkhead box P3+ regulatory T (iTreg) cells. PMID: 25997495
- In the Chinese population, coronary heart disease (CHD) is strongly associated with HLA-DRB1*01 and DRB1*04 haplotypes, and the formation of CD4(+)CD28(null) T cells is linked to HLA-DRB1*01, DRB1*04, and DRB1*15 alleles. PMID: 20842443
- Findings suggest a model for the docking of the full AP-2 tetramer to membranes when bound to Nef, positioning the cytosolic tail of CD4 to interact with its binding site on Nef. PMID: 24473078
- Research demonstrates a null association between the CD4 C868T polymorphism and an individual's susceptibility to HIV-1 acquisition in a Chinese population. PMID: 25611551
- Nicotine alleviates experimental severe acute pancreatitis by enhancing immunoregulation of CD4+ CD25+ regulatory T cells. PMID: 25742430
- T-cell receptor activation of human CD4(+) T cells shifts the innate toll-like receptor response from CXCL8(hi) IFN-gamma(null) to CXCL8(lo) IFN-gamma(hi). PMID: 26205220
- Nef domains involved in CD4 downregulation are essential for activation of plasmacytoid dendritic cells. PMID: 25972534
- This research describes the HIV care cascade and ART delivery supply chain to examine how mathematical modeling can provide insights into cost-effective strategies for scaling-up ART coverage in sub-Saharan Africa and contribute to achieving universal ART coverage. PMID: 25249293
- Rapidly translating new scientific findings into policy is crucial for the HIV response. Adapting and implementing the 2013 WHO treatment recommendations are necessary to prevent unnecessary illness, death, HIV transmission, and associated costs. PMID: 25266850
- This review provides an overview of ART adherence interventions from 2013 to the present, encompassing peer-reviewed journals and abstracts from key conferences. PMID: 25304006
- Early access to combination prevention interventions for key populations, combined with sustained political commitment and a supportive environment for these populations, are essential for maximizing the impact of ART on the HIV epidemic in Vietnam. PMID: 25472886
- The study demonstrates that activated CD4+ T cells can produce 1,25(OH)2D3, and that 1,25(OH)2D3 induces a 2-fold up-regulation of the VDR protein expression in activated CD4+ T cells by protecting the VDR from proteasomal degradation. PMID: 24792400
- Data suggest that CD4 antigen binding disrupts quaternary interactions at the HIV-1 Env trimer apex. PMID: 24931470
- Research explores the multi-faceted role of human SP-D against HIV-1. PMID: 25036364
- The study examines the effects of HIV Nef protein on the downregulation of CD4 and HLA class I in patients with early and chronic HIV infection with HIV-1 subtype C. PMID: 25193656
- This review enhances our understanding of the role of AhR and its signaling pathway in CD4 helper T cell-mediated inflammatory disorders. PMID: 24905409
- Researchers determined that the activation of CD4 through interaction with major histocompatibility complex class II (MHC-II) triggers cytokine expression and the differentiation of human monocytes into functional mature macrophages. PMID: 24942581
- HIV-1 Nef interacts with Alix in late endosomes, which is essential for efficient lysosomal targeting of CD4. PMID: 25118280
- Human tumor-infiltrating CD4+CD69+ T cells suppress T cell proliferation via membrane-bound TGF-beta1. PMID: 24668348
- These findings demonstrate that aptamer-facilitated cell-specific delivery of shRNA represents a novel approach for efficient RNAi delivery and has potential for developing therapeutics targeting specific T cell subtypes. PMID: 25241192
- Data reveal that Ag-specific CD4(+) CD25(+) CD134(+) CD39(+) T cells are highly enriched for Treg cells, constitute a significant component of recall responses, and maintain a Treg-cell-like phenotype upon in vitro expansion. PMID: 24752698
- Binding of the HIV-1 envelope protein gp120IIIB to the CD4/CXCR4/CCR5 heterooligomer was negligible, and gp120-induced cytoskeletal rearrangements necessary for HIV-1 entry were prevented. PMID: 24778234
- Using biopsies from H. pylori-positive patients, PCR was employed to quantify the expression of Foxp3 mRNA, and IHC was utilized to semi-quantify the number of CD4+ CD25+ T cells in the gastric mucosa. PMID: 24901172
- HIV glycoprotein 120 (gp120) requires disulfide reduction in CD4 domain 1 or 2, which impairs thioredoxin-driven CD4 dimerization. PMID: 24550395
- This study identifies a novel mechanism of chronic heat stress immunosuppression mediated by regulating CD4 CD25 Foxp3 Tregs. PMID: 24151582
- The acquisition of B cell stimulating properties by naive cord blood CD4 T cells required the STAT3-dependent expression of ICOS and IL-21. PMID: 23923047
- CD4 retro-translocates with oxidized intrachain disulfide bridges. Only upon proteasomal inhibition does it accumulate in the cytosol as already reduced and deglycosylated molecules. PMID: 24257748
- CD4(+)CD25(+)FOXP3(+) Treg levels were lower in Kawasaki disease patients compared to healthy subjects. Moreover, levels before treatment were lower in intravenous immunoglobulin (IVIg)-resistant patients than in IVIg-sensitive patients. PMID: 23340699
- The CD4(372-433) peptide fragment in the given sample undergoes rotational averaging of anisotropic interactions. Additional amino acid type-specific assignments are achieved for 10 amino acid spin systems for both CD4(372-433) and Vpu. PMID: 23863698
- sCD4 might be considered a significant parameter for rheumatoid arthritis (RA) disease progression with potential diagnostic importance. PMID: 23700441
Database Links
Subcellular Location
Cell membrane; Single-pass type I membrane protein. Note=Localizes to lipid rafts (PubMed:12517957, PubMed:9168119). Removed from plasma membrane by HIV-1 Nef protein that increases clathrin-dependent endocytosis of this antigen to target it to lysosomal degradation. Cell surface expression is also down-modulated by HIV-1 Envelope polyprotein gp160 that interacts with, and sequesters CD4 in the endoplasmic reticulum.
Tissue Specificity
Highly expressed in T-helper cells. The presence of CD4 is a hallmark of T-helper cells which are specialized in the activation and growth of cytotoxic T-cells, regulation of B cells, or activation of phagocytes. CD4 is also present in other immune cells
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