CD40 glycoforms and TNF-receptors 1 and 2 in the formation of CD40 receptor(s) in autoimmunity.

Molecular Immunology
Gisela M Vaitaitis, David H Wagner

Abstract

The CD40-CD154 dyad is an intensely studied field as is glycosylation status and both impact immunological functions and autoimmune conditions. CD40 has several isoforms, is modified by glycosylation, and trimerizes to form the functional receptor. We described a CD4(+)CD40(+) T cell (Th40) subset which is expanded in autoimmunity and is necessary and sufficient in transferring type 1 diabetes. Glycosylation impacts immunological events and T cells from autoimmune mouse strains express 30-40% less GlcNAc-branched N-glycans than T cells from non-autoimmune strains, a decrease known to activate T cells. Here we demonstrate that several CD40 receptor constellations exist on CD4 T cells. However, rather than containing different isoforms of CD40 they contain different glycoforms of isoform I. The glycoform profile is dependent on availability of CD154 and autoimmune NOD mice express a high level of a less glycosylated form. Interestingly, CD40 stimulation induces some CD40 receptor constellations that contain TNF-receptors 1 and 2 and targeting of those alters CD40 signaling outcomes in NOD Th40 cells. CD40-stimulation in vivo of non-autoimmune BALB/c mice expands the Th40 population and alters the CD40 glycoform profile of those c...Continue Reading

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Citations

Sep 17, 2013·Cellular & Molecular Immunology·Gisela M Vaitaitis, David H Wagner
Apr 3, 2014·Journal of Neuroimmunology·Dan M WaidDavid H Wagner
Aug 12, 2014·Diabetologia·Gisela M VaitaitisDavid H Wagner
May 8, 2019·The Journal of Clinical Endocrinology and Metabolism·Gisela M VaitaitisUNKNOWN Type 1 Diabetes TrialNet Study Group
Jun 19, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gisela M VaitaitisDavid H Wagner
Mar 30, 2019·Journal of Neuroimmunology·Gisela M VaitaitisDavid H Wagner

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