The disintegrin domain of ADAM 8 enhances protection against rat experimental autoimmune encephalomyelitis, neuritis and uveitis by a polyvalent autoantigen vaccine.
Targeting peptides have potential as components of recombinant vaccines. Here, we have analyzed a set of structurally diverse peptides fused to a polyepitope vaccine in prevention of rat generalized autoimmunity of the nervous system (GANS), a combined model of experimental autoimmune encephalomyelitis (EAE), neuritis (EAN) and uveoretinitis (EAU). The peptide sequences studied included the endothelial-monocyte-activating polypeptide II (EMAP II), the allograft inflammatory factor-1 (AIF-1), and the interferon-gamma-inducing factor (IGIF, IL-18). Further, a variety of adhesive peptides were tested, including the disintegrin domain of mouse ADAM 8. Interestingly, this disintegrin domain considerably increased the effect of the polyepitope vaccine. Of the other peptides, only IL-18 enhanced tolerance induction, but was less effective than the ADAM 8 disintegrin peptide. In conclusion, disintegrin domains will be valuable leads in the development of targeting peptides for immunointervention.
Institute of Brain Research, University of Tuebingen, Germany.
H J
HJ
Schluesener
D051722:ADAM Proteins; D000818:Animals; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics* / Q000502:physiology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D019483:Disintegrins / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D008666:Metalloendopeptidases; D051379:Mice; D009443:Neuritis / Q000517:prevention & control*; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000517:prevention & control*; D014611:Vaccination
D015703:Antigens, CD; D000954:Antigens, Surface; D001324:Autoantigens; D019483:Disintegrins; D008565:Membrane Proteins; D051722:ADAM Proteins; C489402:Adam8 protein, mouse; D008666:Metalloendopeptidases