CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function

Proceedings of the National Academy of Sciences of the United States of America
Esther Bandala-SanchezLeonard C Harrison

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 of HMGB1. CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR). Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR. This mechanism ma...Continue Reading

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Citations

Sep 12, 2019·Frontiers in Immunology·Abdulrahman M ShathiliNicolle H Packer
Oct 9, 2019·Immunopharmacology and Immunotoxicology·Seyedeh Masoomeh NoorbakhshAbbas Mirshafiey
Nov 13, 2019·Current Pharmaceutical Design·Jacek M WitkowskiTamas Fulop
Jan 23, 2020·Clinical and Experimental Pharmacology & Physiology·Zahra Ashrafi JighehDavoud Sanajou
Aug 14, 2020·International Journal of Cancer. Journal International Du Cancer·Peter AltevogtGlen Kristiansen
Aug 9, 2020·Scandinavian Journal of Immunology·Shrikant S KolanBjørn Steen Skålhegg
Aug 7, 2020·Organic & Biomolecular Chemistry·Levon D Movsisyan, Matthew S Macauley
Mar 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Shoib S SiddiquiAjit Varki
Mar 5, 2021·Frontiers in Immunology·Kartik BhamidipatiWilliam H Robinson
Apr 4, 2021·Cells·Haruki Watanabe, Myoungsun Son
Oct 17, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E-Ming WangMing-Hong Tai

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Methods Mentioned

BETA
surface plasmon resonance
chips

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