KGYY15 is a peptide derived from amino acids 136 to 150 of the mouse protein CD154, a region determined from crystallography and site-directed mutational analysis to interact with CD40, the type I transmembrane protein found on antigen-presenting cells. CD154 is primarily expressed on activated T cells and CD40 - CD154 interactions are critical in the development and perpetuation of autoimmune disease, making CD40 signaling a target in autoimmunity. In addition to interacting with CD40, KGYY15 interacts with the integrins CD11a/CD18 and CD11b/CD18, and the resulting modulation of CD40-CD154 signalling may be more advantageous than complete inhibition. In vivo, KGYY15 is highly efficient in preventing hyperglycaemia in NOD mice that spontaneously develop type 1 diabetes. KGYY15 can also reverse new-onset hyperglycaemia.
