Immune Receptor binding to HLA-B27 licenses immune T cells to trigger Ankylosing Spondylitis

What is it about?

KIR3DL2 binding to HLA-B27 plays a critical role in Ankylosing Spondylitis. We have shown that two molecules found on the surface of immune cells KIR3DL2 and HLA-B27 play a key role in the onset of Ankylosing Spondylitis. When the KIR3DL2 and HLA-B27 (B27) molecules bind each other they promote immune cells called T cells that cause arthritis in Ankylosing Spondylitis (AS) at a key check point early in the production of these cells. KIR3DL2 is also found widely on other immune cells where binding to B27 promotes the production of molecules that cause AS such as IL17. A key molecule involved in switching on pathogenic T cells that make IL17 is a protein called RORgammat. KIR3DL2 binding to B27 switches on RORgammat. Thus, targeting KIR3DL2 binding to B27 could be therapeutically beneficial for treating AS by preventing the T cells that cause disease ever forming in the first place. Whereas conventional treatments for Ankylosing Spondylitis which target molecules like IL17 are effective, targeting B27 binding to KIR3DL2 would be predicted to be a more effective treatment since it would turn off a critical switch for the production of molecules like IL17 so these molecules would never get to be made in the first place. Moreover, since the KIR3DL2-B27 switch occurs early in disease drugs that specifically block this switch would be expected to have fewer side effects than drugs which block the action of molecules like IL17.

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