Structural variants of Bacteroides fragilis-derived alpha-galactosylceramides induce unique natural killer T cell responses.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B671
Abstract ID: 6287

Presenting Author:
Da-Jung Jung , Postdoctoral Fellow at Bigham and Women's Hospital

Abstract:

Natural killer T (NKT) cell is a unique subset of thymus-derived T cells that recognizes glycolipids presented by CD1d molecule expressed on antigen-presenting cells. The most studied agonistic antigen of NKT cells is alpha-galactosylceramide (αGC). It has been shown that structural features of lipid antigens determine distinct NKT cell responses. In order to drive context-dependent NKT cell responses, understanding the structural characteristics of lipid antigens is important. In the previous study, we have shown that human gut symbiont Bacteroides fragilis (B.fragilis) uniquely produces αGCs (BfaGC), which can normalize the overproliferation of neonatal colonic NKT cells in germ-free mice, and chemically-synthesized structural isomers of BfaGCs induce structure-specific NKT cell responses. In this study, to further investigate the essential structural moiety of BfaGC for the unique immunomodulatory activity, we synthesized BfaGC analogues by modifying their chain lengths and functional groups. We have examined how the analogues differently stimulate NKT cells by analyzing in vitro cytokine production, NKT cell proliferation and effect on specific NKT cell subpopulations. We found the critical features and functional groups on the BfaGC structure leading to immunomodulatory responses. It is expected that our findings may advance further development of lipid antigens to fine-tune context-specific NKT cell responses in immunological diseases.