Abstract
Glycosphingolipids (GSLs) are composed of a mono-, di-, or oligosaccharide and a ceramide and function as constituents of cell membranes. Various molecular species of GSLs have been identified in mammalian cells due to differences in the structures of oligosaccharides. The oligosaccharide structure can vary depending on cell lineage, differentiation stage, and pathology; this property can be used as a cell identification marker. Furthermore, GSLs are involved in various aspects of the immune response, such as cytokine production, immune signaling, migration of immune cells, and antibody production. GSLs containing certain structures exhibit strong immunogenicity in immunized animals and promote the production of anti-GSL antibodies. By exploiting this property, it is possible to generate antibodies that recognize the fine oligosaccharide structure of specific GSLs or glycoproteins. In our study using artificially synthesized GSLs (artGSLs), we found that several structural features are correlated with the antibody-inducing activity of GSLs. Based on these findings, we designed artGSLs that efficiently induce the production of antibodies accompanied by class switching and developed several antibodies that recognize not only certain glycan structures of GSLs but also those of glycoproteins. This review comprehensively introduces the immune activities of GSLs and their application as pharmaceuticals.
Highlights
Glycosphingolipids (GSLs) are cell membrane components composed of a mono, di, or oligosaccharide and a ceramide
Several anti-GSL antibodies that recognize certain glycan structures of GSLs have contributed to stem cell research and the diagnosis of various cancers [2]. Pioneering studies in this area revealed that GSLs are immunogenic substances that function as blood group [3] and cancer-associated antigens [2]
A number of antibodies isolated from animals immunized with cancer cells were shown to react with GSLs expressed by those cells, leading researchers to recognize that GSLs are immunogenic substances
Summary
Glycosphingolipids (GSLs) are cell membrane components composed of a mono-, di-, or oligosaccharide and a ceramide. Several anti-GSL antibodies that recognize certain glycan structures of GSLs have contributed to stem cell research and the diagnosis of various cancers [2] Pioneering studies in this area revealed that GSLs are immunogenic substances that function as blood group [3] and cancer-associated antigens [2]. In addition to NS19-9, a number of monoclonal antibodies that recognize certain GSL glycan structures as epitopes have been generated by immunizing host animals with various types of cancer cells. These studies led researchers to realize that GSLs are immunogenic substances
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