An antibody-based construct carrying DNA-mimotope and targeting CR1(CD35) selectively suppresses human autoreactive B-lymphocytes.
There is an urgent and unmet need for therapeutic agents targeting selectively disease-associated B-lymphocytes in autoantibody-mediated diseases. We have constructed a chimeric molecule able to cross-link cell surface immunoglobulin with the inhibitory complement receptor type 1 (CD35) on DNA-specific B cells from SLE (systemic lupus erythematosus) patients with the aim of selectively silencing them. This engineered molecule is made of copies of the DNA-mimotope peptide DWEYSVWLSN coupled to a monoclonal anti-CD35 antibody. We found that the DNA-like peptide chimera induced a dose-dependent decrease in the number of IgG anti-dsDNA antibody producing cells when PBMCs of lupus patients were cultured in its presence. Our data present evidence that clustering BCR and the inhibitory CR1 on disease-associated autoreactive B-lymphocytes selectively suppresses autoantibody production.
Voynova
Elisaveta
E
Department of Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, Bulgaria.
Tchorbanov
Andrey
A
Prechl
Jozsef
J
Nikolova
Milena
M
Baleva
Marta
M
Erdei
Anna
A
Vassilev
Tchavdar
T
D000328:Adult; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000187:drug effects; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D015551:Autoimmunity / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry*; D000939:Epitopes; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000187:drug effects; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008875:Middle Aged; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry*; D017463:Receptors, Complement 3b / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; C509991:CR1 protein, human; D000939:Epitopes; D007074:Immunoglobulin G; D010455:Peptides; D017463:Receptors, Complement 3b; D011993:Recombinant Fusion Proteins; D004247:DNA