A CD40 targeting peptide prevents severe symptoms in experimental autoimmune encephalomyelitis.

CD40/CD154-interaction is critical in the development of Experimental Autoimmune Encephalomyelitis (EAE; mouse model of Multiple Sclerosis). Culprit CD4+CD40+ T cells drive a more severe form of EAE than conventional CD4 T cells. Blocking CD40/CD154-interaction with CD154-antibody prevents or ameliorates disease but had thrombotic complications in clinical trials. We targeted CD40 using a CD154-sequence based peptide. Peptides in human therapeutics demonstrate good safety. A small peptide, KGYY 6 , ameliorates EAE when given as pretreatment or at first symptoms. KGYY 6 binds Th40 and memory T cells, affecting expression of CD69 and IL-10 in the CD4 T cell compartment, ultimately hampering disease development. Unlabelled Image • A CD154-derived, CD40-targeting, peptide (KGYY 6) ameliorates EAE. • KGYY 6 alters the phenotype of CD4 T cells but does not deplete those cells. • Being a peptide, KGYY 6 avoids problems common to antibodies. • KGYY 6 directly targets CD40, not CD154, avoiding possible thrombotic problems. • KGYY 6 does not include the αIIbβ3 interacting domain of CD154. [ABSTRACT FROM AUTHOR]