1/19/2024 0 Comments N linked glycosylation![]() On the other hand, recent literature indicates that Fab glycans may contribute to antibody solubility and stability and may prevent aggregation ( 8– 10). It has been suggested that glycans in the variable domains enhance antibody aggregation ( 5– 7). However, we also observed only minimal or no effects in quite a few cases, suggesting other functions of Fab glycans may exist. We furthermore showed that Fab glycans are usually localized close to antigen-binding sites and can influence antigen binding and contribute to affinity maturation ( 3). We previously showed that these N-glycosylation sites are acquired predominantly at positions in the variable domains where a single nucleotide mutation turns a “latent” or “progenitor” glycosylation motif into an actual N-glycosylation motif. These Fab glycans are acquired following introduction of N-glycosylation sites during somatic hypermutation and thereby constitute part of the physiological repertoire of antibodies ( 2). Fab glycans are present in about 15% of circulating IgGs ( 1). IgGs can contain N-linked glycans in the variable domains, the so-called Fab glycans (Figure 1), in addition to the Fc glycans in the C H2 domains. Immunoglobulin G (IgG) is the most abundant class of immunoglobulins in human serum. These findings indicate that introducing Fab glycans may represent a mechanism to improve therapeutic/diagnostic antibody stability. Collectively, our data show that variable domain N-linked glycans acquired during somatic hypermutation can contribute to IgG antibody stability. Strikingly, removal of Fab glycans naturally acquired during antigen-specific immune responses can deteriorate antibody stability, suggesting in vivo selection of stable, glycosylated antibodies. By analyzing thermal unfolding profiles of antibodies with or without Fab glycans, we demonstrate that introduction of Fab glycans can improve antibody stability. We investigated whether Fab glycans may-in addition to affecting antigen binding-contribute to antibody stability. These Fab glycans are acquired following introduction of N-glycosylation sites during somatic hypermutation and contribute to antibody diversification. Immunoglobulin G (IgG) can contain N-linked glycans in the variable domains, the so-called Fab glycans, in addition to the Fc glycans in the C H2 domains. ![]() 4Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, United States.3Academic Medical Centre, Department of Medical Microbiology, University of Amsterdam, Amsterdam, Netherlands.2Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.1Sanquin Research, Department of Immunopathology, Amsterdam, Netherlands.de Taeye 1,2,3 Pleuni Ooijevaar-de Heer 1,2 Rogier W. ![]()
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