Journal article
CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function
E Bandala-Sanchez, NG Bediaga, ED Goddard-Borger, K Ngui, G Naselli, NL Stone, AM Neale, LA Pearce, A Wardak, P Czabotar, T Haselhorst, A Maggioni, LA Hartley-Tassell, TE Adams, LC Harrison
Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2018
Abstract
CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function. We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1). CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10. Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain o..
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Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Dr. Ajit Varki for helpful discussions. This work was supported by Australian National Health and Medical Research Council (NHMRC) Program Grant 1037321 and the Walter and Eliza Hall Institute Catalyst Fund. L.C.H. is the recipient of a NHMRC Senior Principal Research Fellowship 1080887. We acknowledge TrendBio for access to the automated, quantitative Western blot analysis instrument (WES) system. The work was made possible through Victorian State Government Operational Infrastructure Support and NHMRC Research Institute Infrastructure Support Scheme.