Suppression of allergen-specific B lymphocytes by chimeric protein-engineered antibodies

Kerekov, Nikola; Michova, Antoaneta; Muhtarova, Maryia; Nikolov, Georgi; Mihaylova, Nikolina; Петрунов, Богдан; Nikolova, Maria; Tchorbanov, Andrey

doi:10.1016/j.imbio.2013.07.009

Cited by 7 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fixing the allergen with two adjacent molecules of IgE associated with mast cells is a trigger of an allergic reaction. 22 Wang Z et al observed that the serum levels of IgE were signifi cantly higher in patients with diabetes and…”

Section: Resultsmentioning

confidence: 99%

Association between Type 2 Diabetes, Obesity and Key Immunological Components of IgE-mediated Inflammation

Sokolova¹,

Yankova²,

Abadjieva³

et al. 2017

Folia Medica

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Association between Type 2 Diabetes, Obesity and Key Immunological Components of IgE-mediated Inflammation

Sokolova¹,

Yankova²,

Abadjieva³

et al. 2017

Folia Medica

View full text Add to dashboard Cite

show abstract

“…The second chimeric molecule contained copies of the Der p 1‐derived peptide sequence (p52–71) from Dermatophagoides pteronyssinus coupled to the same anti‐human CD35 antibody. We have shown that Der p 1‐peptide chimeric molecules cross‐linked Der p 1‐specific BCR with CD35 on the allergen‐specific B cells from HDM allergy patients, resulting in the significant reduction of anti‐Dpt IgE antibody‐producing plasma cells .…”

Section: Discussionmentioning

confidence: 99%

“…The chimeric molecules were constructed by separate conjugation of peptides to anti‐CD35 (clone 3D9) antibodies using the zero‐length cross‐linking agent EDC [1‐ethyl‐3‐(3′‐dimethylaminopropyl) carbodiimide.HCl] (Sigma‐Aldrich, Taufkirchen, Germany), as described previously . Briefly, for the initiation of the protein conjugation, a lysine carrying Ahx linker was introduced to the C‐end of the peptides during the peptide synthesis.…”

Section: Methodsmentioning

confidence: 99%

“…that the human CD35 can provide a strong inhibitory signal to human B lymphocytes . We have previously shown that the binding of specific epitopes to the B cell receptors and the cross‐linking with CD35 on the surface of autoreactive cells may have a strong negative effect on them . The goal of our research is to selectively suppress anti‐GAD65 IgG antibody‐producing B lymphocytes from T1DM patients by chimeric protein molecules that contain a monoclonal antibody, specific to CD35 conjugated to peptide epitopes from GAD65.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protein-engineered molecules carrying GAD65 epitopes and targeting CD35 selectively down-modulate disease-associated human B lymphocytes

Manoylov

Boneva

Doytchinova

et al. 2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Type 1 diabetes mellitus is an autoimmune metabolic disorder characterized by chronic hyperglycemia, the presence of autoreactive T and B cells and autoantibodies against self‐antigens. A membrane‐bound enzyme on the pancreatic beta‐cells, glutamic acid decarboxylase 65 (GAD65), is one of the main autoantigens in type 1 diabetes. Autoantibodies against GAD65 are potentially involved in beta‐cell destruction and decline of pancreatic functions. The human complement receptor type 1 (CD35) on B and T lymphocytes has a suppressive activity on these cells. We hypothesized that it may be possible to eliminate GAD65‐specific B cells from type 1 diabetes patients by using chimeric molecules, containing an anti‐CD35 antibody, coupled to peptides resembling GAD65 B/T epitopes. These molecules are expected to selectively bind the anti‐GAD65 specific B cells by the co‐cross‐linking of the immunoglobulin receptor and CD35 and to deliver a suppressive signal. Two synthetic peptides derived from GAD65 protein (GAD65 epitopes) and anti‐CD35 monoclonal antibody were used for the construction of two chimeras. The immunomodulatory activity of the engineered antibodies was tested in vitro using peripheral blood mononuclear cells (PBMCs) from type 1 diabetes patients. A reduction in the number of anti‐GAD65 IgG antibody‐secreting plasma cells and increased percentage of apoptotic B lymphocytes was observed after treatment of these PBMCs with the engineered antibodies. The constructed chimeric molecules are able to selectively modulate the activity of GAD65‐specific B lymphocytes and the production of anti‐GAD65 IgG autoantibodies by co‐cross‐linking of the inhibitory CD35 and the B cell antigen receptor (BCR). This treatment presents a possible way to alter the autoimmune nature of these cells.

show abstract

“…The three chimeras were engineered by separate chemical coupling of the peptides to anti-CR1 antibody as previously described [ 17 , 41 ]. Briefly, the monoclonal antibody and peptide solutions were mixed at a 20-fold molar excess of the peptides, and a zero-length crosslinking agent EDC (1-ethyl-3-(3′-dimethylaminopropyl) carbodiimide.HCl), (Sigma) was added for initiation of the coupling reaction at a 60-fold molar excess relative to the antibody.…”

Section: Methodsmentioning

confidence: 99%

Selective Silencing of Disease-Associated B Lymphocytes from Hashimoto’s Thyroiditis Patients by Chimeric Protein Molecules

Ralchev

Markovski

Yankova

et al. 2022

IJMS

View full text Add to dashboard Cite

Hashimoto’s thyroiditis is one of the most common endocrine disorders, affecting up to 20% of the adult population. No treatment or prevention exists except hormonal substitution for hypothyroidism. We hypothesize that it may be possible to selectively suppress anti-thyroglobulin (Tg) IgG antibody-producing B lymphocytes from HT patients by a chimeric protein molecule containing a monoclonal antibody specific for the human inhibitory receptor CR1, coupled to peptide epitopes derived from Tg protein. We expect that this treatment will down-regulate B-cell autoreactivity by delivering a strong inhibitory signal. Three peptides—two epitope-predicted ones derived from Tg and another irrelevant peptide—were synthesized and then coupled with monoclonal anti-human CR1 antibody to construct three chimeric molecules. The binding to CD35 on human B cells and the effects of the chimeric constructs on PBMC and TMC from patients with HT were tested using flow cytometry, ELISpot assay, and immunoenzyme methods. We found that after the chemical conjugation, all chimeras retained their receptor-binding capacity, and the Tg epitopes could be recognized by anti-Tg autoantibodies in the patients’ sera. This treatment downregulated B-cell autoreactivity and cell proliferation, inhibited Tg-specific B-cell differentiation to plasmablasts and promoted apoptosis to the targeted cells. The treatment of PBMCs from HT patients with Tg-epitope-carrying chimeric molecules affects the activity of Tg-specific autoreactive B lymphocytes, delivering to them a strong suppressive signal.

show abstract

Suppression of allergen-specific B lymphocytes by chimeric protein-engineered antibodies

Cited by 7 publications

References 33 publications

Association between Type 2 Diabetes, Obesity and Key Immunological Components of IgE-mediated Inflammation

Association between Type 2 Diabetes, Obesity and Key Immunological Components of IgE-mediated Inflammation

Protein-engineered molecules carrying GAD65 epitopes and targeting CD35 selectively down-modulate disease-associated human B lymphocytes

Selective Silencing of Disease-Associated B Lymphocytes from Hashimoto’s Thyroiditis Patients by Chimeric Protein Molecules

Contact Info

Product

Resources

About