Anti-glycan natural antibodies
The innate immunity system has been much less studied compared to the adaptive immunity, this being also true for the humoral component of innate immunity, i.e. natural antibodies. Natural antibodies are produced by the population of long-living B-1 lymphocytes representing 25-30% of the total number of B cells. B-1 cells matures considerably earlier than B-2 cells and exist for life. Immunoglobulins against glycans constitutes a considerable (possibly prevailing) part of human natural antibodies. Their presence in practically all healthy persons and high content in peripheral blood give evidence of biological significance. At the same time their specific targets, mechanism of action, and genesis remain unclear; it is also unclear whether the (a part of them) are autoantibodies. The understanding of the mechanisms of B-1 cells functioning is necessary for creation of a general pattern of immune system action; basic research in this field will obviously lead to the development of principally new strategies of therapy and diagnostics. The main task of this project is the study of several anti-glycan antibodies most abundant in human blood, revealing of the molecular nature of their targets, their biological role, and structure-function study of immunoglobulin glycosylation, and participation of the glycans in antigen-binding and effector functions of natural antibodies. An additional task is meaningful explanation of the observed lack of autoimmune reaction of this group of antibodies with cells and tissues having in composition the cognate glycans. The result of this study will be an experimental verification of our hypothesis on that anti-glycan natural antibodies are directed against inner (masked on cell surface) sites of carbohydrate chains and/or their patterns, thus eliminating cancer cells without interaction with normal ones. The discussed above natural anti-glycan antibodies were isolated and characterized for the first time by the research group of this project.
January 6, 2014 December 31, 2016
List of publications
- (2019). Synthesis of blood group Forssman pentasaccharide GalNAcα1-3GalNAcβ1-3Galα1-4Galβ1-4Glcβ–R. MENDELEEV COMMUN 29 (5), 578–580
- (2023). Removal of natural anti-αGal antibodies elicits protective immunity against Gram-negative bacterial infections. Front Immunol 14, 1232924
- (2015). Interactions of antitumour Sialyl Lewis X liposomes with vascular endothelial cells. BIOCHIM BIOPHYS ACTA 1848 (5), 1099–1110
- (2015). A diverse range of bacterial and eukaryotic chitinases hydrolyzes the lacNAc (galβ1-4GlcNAc) and lacdinac (GalNAcβ1-4GlcNAc) motifs found on vertebrate and insect cells. J Biol Chem 290 (9), 5354–5366
- (2015). Synthesis of 1-BODIPY-labeled 2-amino-2-deoxy-d-glucose, substrate for acetyl-CoA:glucosaminide N-acetyltransferase. MENDELEEV COMMUN 25 (6), 422–423
- (2015). Comparative lectinology: Delineating glycan-specificity profiles of the chicken galectins using neoglycoconjugates in a cell assay. Glycobiology 25 (7), 726–734
- (2015). The synthesis of oligosaccharides containing internal and terminal Galβ1-3GlcNAcβ fragments. Russ. J. Bioorganic Chem. 41 (2), 147–160
- (2015). Glycomapping the fine specificity of monoclonal and polyclonal Lewis antibodies with type-specific Lewis kodecytes and function-spacer-lipid constructs printed on paper. Transfusion 56 (2), 325–333
- (2015). Hypotheses of the origin of natural antibodies: A glycobiologist's opinion. Biochemistry (Mosc) 80 (7), 820–835