N-glycosylation of MHCII alters presentation of commensal carbohydrate antigens (100.24)

Abstract

Abstract In conditions of dysregulated inflammatory responses, such as inflammatory bowel disease, recent studies have suggested that oral treatment with the capsular polysaccharide A (PSA) from the intestinal commensal Bacteroides fragilis promotes regulatory CD4 T cells and reduces disease pathology, yet the endogenous mechanisms of PSA immune activation remain unclear. Unlike traditional T cell-independent polysaccharide antigens, we have characterized a group of T cell-dependent antigens (T-glycoantigen) including PSA that are processed and presented within the MHCII pathway for CD4 T cell recognition. However, unlike prototypical peptide antigens, we have found that T-glycoantigen presentation is sensitive to the N-glycosylation state of MHCII. Furthermore, we have defined a key glycosyltransferase in antigen presenting cells that is necessary for T-glycoantigen presentation, but is dispensable for peptide antigen. We have translated this discovery into a novel mouse model to define the mechanisms behind the potential therapeutic role of PSA-specific T cell responses in health and disease. Our results provide evidence for the role of B. fragilis colonization in immune homeostasis and its potential use as a “probiotic” therapy to modulate dysregulated immune systems in inflammatory diseases. (Supported by grants OD004225 and GM082916 to BA Cobb)