A Spoonful of Glycan-Specific Natural Antibodies Helps Autoimmunity Go Down

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From Mary Poppins to Asvaghosa, the idea that sugar plays an important role in medicine seems a nearly universal trope. When it comes to immune tolerance, it seems that it is not far from the truth. Together with nucleic acids, proteins, and lipids, complex carbohydrates (glycans) are fundamental to the normal physiology of living organisms. Glycans mediate cellular interactions that include intracellular protein trafficking, intercellular communication, and microbial pathogenesis. They are also used by the immune system to differentiate self- from pathogenic molecules during bacterial infections, and the presence of anti-glycan antibodies in serum serves for the diagnosis and prognosis of multiple autoimmune diseases. Despite the well-known role of anti-glycan antibodies in autoimmunity, studies in immune tolerance make it clear that organisms can develop responses to self-antigens without triggering an autoimmune disease. As such, glycan-specific antibodies of different immunoglobulin sub-classes are present during homeostasis in the serum of healthy humans and mice. Likewise, different types of immune cells interact with self- and foreign-glycans inside and outside of an inflammatory context and their recognition can trigger or inhibit innate and adaptive immune responses. Yet, little is known on how immune responses that target a self-glycan in a foreign entity are possible without triggering an autoimmune reaction. Here, we exploit techniques from biomolecular engineering, such as engineered outer membrane vesicles and yeast surface display, to understand how the context in which a glycan is presented to the immune system can change a canonical T-cell independent immune response to a T-cell dependent immune response, as well as the role of natural antibodies in preventing autoimmunity. As a whole, this thesis aims to review what we know about the humoral innate and adaptive immune responses to both self and foreign glycans, the involvement of tertiary lymphoid tissues in the temporal response to self-glycans, and how we can technologically exploit glycoimmunology for the development of anti-glycan antibodies.

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anti-glycan antibodies; antibody discovery; B1 cells; glycan immune response; natural antibodies; polysialic acid


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Union Local


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DeLisa, Matthew

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Paszek, Matthew
Koretzky, Gary
Clark, Theodore

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Chemical Engineering

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Ph. D., Chemical Engineering

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Doctor of Philosophy

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Government Document




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Attribution-NonCommercial 4.0 International


dissertation or thesis

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