University of Cambridge > > Seminars at the Department of Biochemistry > The glycobiology of antibodies, Fc receptors and the immune response

The glycobiology of antibodies, Fc receptors and the immune response

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ABSTRACT Therapeutic antibodies have had great success in cancer and autoimmune disease treatment and developments in antibody drug conjugates and bi-specifics continue to enhance patient treatment options. Immunoglobulin G antibodies are modified by the addition of conserved glycan chains to the antibody Fc region, a modification critical for antibody interactions with the immune system and induction of effector activities such as complement activation, phagocytosis and ADCC . Communication of IgG antibodies with the immune system is controlled and mediated by Fc gamma receptors (FcγR), membrane bound glycoproteins that relay the information sensed and gathered by antibodies. These glycoprotein receptors act as a link between the innate and adaptive immune systems and there is now clear evidence that FcγR glycosylation is also an important factor in the interaction with antibodies and immune system activation or inhibition. Little is known, however, about how these receptors are glycosylated in their natural environment by cells of the immune system, in healthy and disease states. Through glycan analysis and sequencing we have shown that FcγR glycosylation is complex, differential depending on the receptor subtype and cell type specific. This has intriguing implications for how antibodies interact with cells of the immune system. Through biophysical interaction experiments we have shown that glycosylation of FcγRs is a critical component of the antibody interaction and specific receptor glycoforms play a key role to promote or inhibit a productive molecular engagement of antibody and receptor. We believe this to be a mechanism used by the immune system to fine-tune the antibody mediated immune response, to enhance or inhibit the interaction of antibodies and alterations in the balance of Fc gamma receptor glycosylation can potentially lead to inflammation and autoimmune disease.

This talk is part of the Seminars at the Department of Biochemistry series.

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