Therefore, it seems reasonable to assume that some of them perform specific functions, such as blocking (masking) antigens in allergy [52,53] or pregnancy [54], to abolish the effector function, thus preventing inflammatory reactions. == Acknowledgments == We thank Holly Perry for the helpful suggestions and fruitful discussions. == Supplementary Materials == The following supporting information can be downloaded athttps://www.mdpi.com/article/10.3390/antib13040105/s1, Supplementary Material File S1; Supplementary Material File S2. == Author Contributions == N.S.: conceptualization, data curation, methodology, software, funding acquisition, visualization, writingoriginal draft, writingreview and editing, project administration. human serum, and, in the presence of the complement, it lysed red blood cells coated with the same glycan (kodecytes, where glycans expressed on biological membranes), while an isolated complement non-activating antibody did not, which confirms the validity of the solid-phase PGA results.Conclusions.Thus, ~30% of human anti-glycan antibodies lack the ability to activate the complement system. The function of the widely represented immunoglobulins that do not cause C3 deposition remains unclear. Keywords:printed glycan array, anti-glycan antibodies, complement,O-antigens, polysaccharides, kodecytes == 1. Introduction == A common component involved in all three (classical, alternative and lectin) pathways of the complement system is the C3 protein, which is usually activated with the participation of the C3-convertase C4b2b in the classical and lectin pathways, or C3bBb in the alternative pathway [1,2]. As a result of proteolysis, C3 converts into C3a and C3b, the latter reacting with the Fab region of immunoglobulins but also binding to cell surfaces. C3b is then either split further (deactivated) by the contribution of factors H and I into the component C3d [2,3] or, if not inactivated, becomes part of the C5 convertase of the classical and lectin pathways C4b2b3b, or the alternative C5 convertase C3bBb3b, and complement activation can continue to the final stage of cell lysis via binding of C6C9 and formation of the membrane attack complex C5b-9. Antibodies are involved in all three pathways of complement activation: classical (by binding the C1q component with their Fc region), 7-Methyluric Acid alternative (due to spontaneously formed C3b capable of attaching to immunoglobulin) [4] and, indirectly, lectin (due to interactions of mannan-binding lectin (MBL) with glycans present on IgG or IgA, but not IgM) [5,6,7,8]. C3b bound to immunoglobulins around the cell membrane interacts with the complement receptor on follicular dendritic cells and B cells (CR2 receptor), as well as macrophages (CR3 and CR4 receptors), activating them and facilitating the presentation of the recognized antigen [2,9,10]. Naturally occurring 7-Methyluric Acid antibodies, i.e., immunoglobulins that appear in the organism without an obvious pathogen-specific stimulation of the immune system and make up the majority of antibodies in healthy human blood (which also includes the adaptive ones), are also actively involved in the complement cascade [11,12,13]. Antibodies to mono-, oligo- or polysaccharides, as well as to glycopeptides (anti-glycan antibodies, AGAs), a representative part of the total pool of natural antibodies, are no exception [12,13]. For example, it is usually well known that complement-mediated hemolysis can occur in the case of ABO-mismatched blood transfusion [14]. Upon xenotransplantation, antibodies to the so-called Gal antigen and Hanganutziu-Deicher, HD (Neu5Gc2-3Gal1-4Glc) antigen, trigger the complement cascade, causing acute tissue/organ rejection [15,16,17,18]. Anti-bacterial 7-Methyluric Acid immunoglobulins directed towards rhamno-lipopolysaccharides and capable of activating the complement have been well studied [19]. It should be noted that very high titers of antibodies to the Rha monosaccharide are found in human blood [20,21]. To date, several hundred different specificities of anti-glycan antibodies are known [20,21,22]; however, whether all of them are capable of activating the complement system is unknown. In this work, using a printed glycan array made up of 605 glycoligands (oligo- and polysaccharides, glycopeptides), we analyzed the ability of human blood AGAs (IgG and IgM) to initiate the deposition of C3 and investigated whether some of these antibodies can also lyse red blood cells (RBCs) in a complement-dependent manner (thus showing whether Rat monoclonal to CD4.The 4AM15 monoclonal reacts with the mouse CD4 molecule, a 55 kDa cell surface receptor. It is a member of the lg superfamily,primarily expressed on most thymocytes, a subset of T cells, and weakly on macrophages and dendritic cells. It acts as a coreceptor with the TCR during T cell activation and thymic differentiation by binding MHC classII and associating with the protein tyrosine kinase, lck the solid-phase PGA results have some equivalence with what would happen on a biological membrane). == 2. Materials and Methods == == 2.1. Serum Samples == Sera and red blood cells from healthy adult blood donors were obtained from the Sechenov First Moscow State Medical University Blood Center according to standard clinical and laboratory rules of the Russian Federation. All subjects gave written informed consent form approved by the local ethics committee of I.M. Sechenov First Moscow State Medical University ( 07-17, 13 September 2017, Moscow, Russia). The characteristics of the donors are.