CR1 Recombinant Monoclonal Antibody
Description
Production and Engineering of CR1-rmAbs
CR1-rmAbs are synthesized using recombinant DNA technology, enabling precise epitope targeting and scalable production. Key methodologies include:
Recombinant Expression Systems
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Vector Design: CR1-rmAbs are cloned into plasmid vectors, often incorporating multimerizing domains (e.g., C4 binding protein α-chain) to enhance stability and functional activity .
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Immunogen Selection: Synthetic peptides derived from CR1’s extracellular domain (e.g., SCR29-30) serve as immunogens to generate antibodies with desired specificity .
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Host Systems: Mammalian cells (e.g., CHO) are commonly used for production, yielding soluble, homogeneous molecules .
Heteromultimeric Constructs
For therapeutic applications, CR1-rmAbs are fused with targeting moieties (e.g., single-chain Fv anti-Rh(D)) to anchor CR1 to erythrocytes, restoring or enhancing CR1 density . This approach leverages the C-terminal multimerizing domain of C4 binding protein to form covalently linked, soluble molecules .
Mechanistic Insights
CR1-rmAbs modulate complement activity and immune complex clearance via:
Complement Regulation
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Cofactor Activity: CR1 facilitates factor I-mediated cleavage of C3b and C4b, inhibiting complement activation .
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Immune Complex Clearance: CR1-rmAbs mimic native CR1’s clustering on erythrocytes, enhancing immune complex binding and transport to the liver/spleen .
Epitope Specificity
Research Applications and Findings
CR1-rmAbs have been extensively studied in immunological and clinical contexts:
Diagnostic Utility
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CR1 Quantification: CR1-2B11 avoids epitopes affected by CR1’s structural polymorphism, enabling precise RBC CR1 enumeration .
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Flow Cytometry: Quantitative flow cytometry using CR1-rmAbs reveals CR1 density variations in diseases like systemic lupus erythematosus (SLE) .
Therapeutic Potential
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Immune Complex Diseases: Heteromultimeric CR1-rmAbs restore CR1 density on papain-treated erythrocytes, mimicking native clustering and enhancing immune complex uptake .
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Kidney Injury Models: Truncated CR1 variants (e.g., CSL040) show enhanced in vivo stability and efficacy in reducing immune complex-mediated renal damage .
Malaria Resistance
CR1 binds Plasmodium falciparum PfRh4, a ligand critical for erythrocyte invasion. Soluble CR1 competitively inhibits PfRh4 binding, suggesting a role in malaria protection .
Disease Associations
Challenges
Product Specs
The CR1 recombinant monoclonal antibody is generated through a meticulous process. Antibody genes are retrieved from B cells of immunoreactive rabbits, amplified, and cloned into appropriate phage vectors. These vectors are then introduced into mammalian cell lines, enabling the production of functional antibodies. The CR1 recombinant monoclonal antibody is subsequently isolated from the culture supernatant of the transfected cell lines and purified through affinity chromatography. After rigorous verification, the antibody is ready for use in ELISA and IHC applications, facilitating precise detection of human CR1 protein.
Complement Receptor type 1 (CR1) is a multifaceted receptor crucial for regulating the complement system. Its functions encompass complement cascade regulation, opsonization, immune complex clearance, immune tolerance, and safeguarding host cells from complement-mediated damage. It is a vital component of both innate and adaptive immune responses.
Target Background
- This study correlated phenotypic data (CR1 density per erythrocyte (CR1/E), blood soluble CR1 (sCR1)) with genetic data (density/length polymorphisms) in AD patients and healthy controls. PMID: 30044434
- CR1 rs1704660G, rs17047661G, and rs6691117G variants were significantly associated with Chagas disease. PMID: 29323238
- Meta-analysis validated the association of late-onset Alzheimer disease with CR1 (rs6656401) variants. PMID: 29504051
- rs6656401 CR1 is not associated with late-onset Alzheimer's disease. PMID: 28477215
- CR1 plays a vital role in Alzheimer's disease pathology and disease progression. PMID: 26742530
- The effect of CR1 rs3818361 polymorphism on Alzheimer's disease (AD) risk in Chinese cohorts is consistent with the increased risk observed in European AD cohorts. PMID: 26189835
- Genetic variation within the CR1 gene is associated with inflammation and the risk of incident coronary artery disease. PMID: 28033544
- The distribution of the CR1 alleles, genotypes, and haplotypes differed significantly among populations in Brazil, Vietnam, India, Republic of Congo, and Ghana. PMID: 28520715
- CD16 and CD35 are important for neutrophil internalization of M. tuberculosis, whereas HIV-1 infection adversely affects opsonophagocytosis. PMID: 27258232
- This study demonstrates an up-regulation of complement regulatory proteins, CD35 and CD55, in HIV-associated pre-eclamptic compared to normotensive pregnancy. PMID: 27521598
- Although B lymphocytes of active systemic lupus erythematosus (SLE) patients express lower levels of CR1, the inhibitory capacity of this complement receptor is still maintained, and its ligand-induced clustering results in significant inhibition of the main B cell functions, similar to that found in healthy individuals. PMID: 27981054
- CyaA binding did not trigger downstream signaling of CR3 in human monocytes, and CyaA-catalyzed elevation of cAMP effectively blocked CR3 signaling initiated by a natural ligand. PMID: 26650353
- The Putative Role of CR1 in Alzheimer's Disease PMID: 26914463
- Knops blood group antigen a/b genotype was associated with increased susceptibility to severe malaria, and the b/b genotype was associated with reduced risk of severe malaria. PMID: 25916414
- The C4d/CR1 ratio is a simple and quickly determinable biomarker that enables the differentiation between infection and flare-up in febrile SLE patients at initial evaluation. PMID: 26273660
- This meta-analysis further supports previous findings that the CR1 rs6656401 polymorphism contributes to Alzheimer's Disease susceptibility. PMID: 24878768
- Complement receptor type 1 (CR1/CD35) expressed on activated human CD4+ T cells contributes to the generation of regulatory T cells. PMID: 25742728
- These results provide a framework for understanding how loss of CR1 expression on podocytes may contribute to complement-mediated damage in the kidney. PMID: 26260209
- Findings provide evidence that the A carrier (AG/GG) and the A allele of the ECR1 A3650G polymorphism may be correlated to the pathogenesis of NRDS and, hence, might be involved in the susceptibility to NRDS. PMID: 25494101
- THE COMBINATION OF EXPRESSION OF MARKERS CR1 AND CR2 (CD35/CD21) IN DIAGNOSTIC OF B-CELL LYMPHOPROLIFERATIVE DISEASES PMID: 26189291
- CR1 gene rs2274567 G/A, rs4844600 G/A, and rs2296160 C/T polymorphisms may not be involved in susceptibility to malaria in the Chinese population. PMID: 25683978
- In addition to being a risk factor for Alzheimer's disease development, a CR1 SNP appears to be associated with higher rates of medium-term disease progression. PMID: 24998857
- Data indicate that complement activation promotes complement component 3 C3b deposition on native and acetylated LDL and binding to the complement receptor 1 (CR1). PMID: 25349208
- A meta-analysis demonstrated significant associations of both the CR1 rs6656401 and CR1 rs3818361 polymorphisms with late-onset Alzheimer's disease susceptibility. PMID: 24996192
- CR1 SNPs correlate with specific aspects of cognitive impairment in Alzheimer's disease patients. PMID: 24530172
- This study identified nominally significant or suggestive associations between the LOAD-risky CR1 variants and worse Logical Memory immediate recall scores in blacks. PMID: 23643458
- Increased CR1 expression was associated with histology classification. PMID: 23464487
- CR1 rs7525160 G > C polymorphism was associated with an increased risk of developing non-small cell lung cancer in the Chinese population. PMID: 24621201
- Polymorphism of the complement receptor 1 gene correlates with the hematologic response to eculizumab in patients with paroxysmal nocturnal hemoglobinuria. PMID: 24038027
- This is the first study to elucidate the relationship of the L-CR1 transcript with the disease activity of RA patients. PMID: 24433281
- Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor. PMID: 24214979
- Maternal coding variants in complement receptor 1 are associated with spontaneous idiopathic preterm birth. PMID: 23591632
- Two Alzheimer's disease-associated CR1 variants, rs6656401 and rs3818361, are associated with major recurrent depression in females in a population-based cohort using individuals from the Generation Scotland: Scottish Family Health Study. PMID: 22244847
- It did not explain (part of) the association of genome-wide association top single-nucleotide polymorphisms rs3818361/rs6656401, nor of the CR1 copy number variation, with Alzheimer disease in our cohort. PMID: 23582656
- ATP release following CR1 ligation increases the mobility of the lipid fraction of RBC membranes, which in turn facilitates CR1 clustering, and thereby enhances the binding avidity of complement-opsonized particles to the RBC CR1. PMID: 24022490
- Data show that increased CD35, CD46, CD55, and CD59 on neutrophils and monocytes present potent markers of bacterial infection and viral infection. PMID: 23376460
- The CD35 antigen bounds gp350/220 and became latently infected when the fusion receptor HLA II was coexpressed. PMID: 23416052
- Genome-wide association studies found 3 new susceptibility loci for Alzheimer disease (AD): complement receptor 1, clusterin, and the phosphatidylinositol-binding clathrin assembly protein. These SNPs are not associated with AD in a Polish population. PMID: 23650005
- Our findings suggest complex mechanisms underlying the interaction of CR1, APOE, and brain amyloid pathways in Alzheimer disease. PMID: 23022416
- Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheumatoid arthritis patients. PMID: 22962438
- We identified rare small events overlapping CR1 and BIN1 in Alzheimer's disease and normal controls with opposite copy number variation dosage. PMID: 23202439
- Malaria inhibits surface expression of complement receptor 1 in monocytes/macrophages, causing decreased immune complex internalization. PMID: 23440418
- There are fewer mono- or dinucleated, but dramatically more numbers of tri- or polynucleated megakaryocytes in the bone marrow of transgenic Crry mice. PMID: 23390291
- Common CR1 variants significantly protect against severe malaria in an endemic area. PMID: 23152904
- In conclusion, despite there are some limitations, this meta-analysis indicates that the A allele of the CR1 SNP rs6656401 is significantly associated with LOAD susceptibility in Chinese Han populations. PMID: 22960360
- The clustering phenomenon of CR1 in erythrocytes is identified in electron microscopy. PMID: 22374251
- Our results support that the CR1-S isoform explains the GWAS signals and open a novel prospect for the investigation of CR1-related disease mechanisms. PMID: 22819390
- Simultaneous quantitative analysis of CD64 and CD35 expression on neutrophils might be useful to distinguish between bacterial and viral infections in rheumatoid arthritis patients. PMID: 22237765
- CR1 (CD35) and CR3 (CD11b/CD18) act in concert for phagocytosis of opsonized Francisella tularensis by human neutrophils. PMID: 22888138
- CLU and CR1 were associated with more rapid cognitive decline. PICALM was associated with an earlier age at midpoint of cognitive decline. PMID: 22952074
