Massachusetts General Hospital
Center for Immunology and Inflammatory Diseases
149 13th Street, Room 8.307
Charlestown, MA 02129
Immunoglobulin gamma (IgG) antibodies are the preeminent effector proteins of the immune system. They recognize antigens with high affinity and specificity, and have an extended circulation half-life of 14 days. IgG are indispensable for immunological memory following pathogen exposure or vaccination, bridging the adaptive and innate immune system for clearance of microbes. The bimodal activity of IgG allows simultaneous recognition of antigen (by the antigen-binding fragment, Fab), and recruitment and activation of leukocytes through engagement of the constant, crystallizable fragment (Fc) with Fc γ receptors (FcγRs). A single, N-linked glycan is attached to each heavy chain of IgG antibodies in the constant domain. Over 30 distinct Fc glycans have been described in healthy individuals, indicated the tremendous heterogeneity of the IgG Fc glycan. Importantly, the composition of this glycan has profound effects on antibody biology. The addition of the sugar moiety sialic acid to the terminus of the glycan converts IgG antibodies into anti-inflammatory mediators, capable of suppressing autoimmune inflammation. Sialylated IgG antibodies loose the ability to bind canonical FcγRs, and instead interact with the C-type lectin, DC-SIGN, triggering a potent anti-inflammatory cascade. Less than 10% of IgG antibodies in healthy individuals are sialylated, and these levels are markedly reduced during inflammatory conditions, including the autoimmune diseases rheumatoid arthritis and Wegener’s granulomatosis. The overarching goal of my laboratory is to understand the interplay of the immune system and glycosylation. We hope to understand how the immune system regulates glycosylation, and how the interactions of glycoproteins and their lectin receptors can alter immune responses.
Anthony RM, Kobayashi T, Wermeling F, Ravetch JV. Intravenous gammaglobulin suppresses inflammation through a novel T(H)2 pathway. Nature. 2011; 475(7354): 110-3.
Anthony RM, Wermeling F, Karlsson MC, Ravetch JV. Identification of a receptor required for the anti-inflammatory activity of IVIG. Proc Natl Acad Sci U S A. 2008; 105(50): 19571-8.
Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV. Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science. 2008; 320(5874): 373-6.
Anthony RM, Wermeling F, Ravetch JV. Novel roles for the IgG Fc glycan. Annals of the New York Academy of Sciences. 2012; 1253: 170-80
For a complete listing of publications click here.
Last Update: 1/6/2014