Cytokine-neuroantigen fusion proteins: new tools for modulation of myelin basic protein (MBP)-specific T cell responses in experimental autoimmune encephalomyelitis.
Fusion proteins incorporating anti-inflammatory cytokines and immunodominant self antigen as separate domains of a single protein may hold promise for development of antigen-specific tolerogenic vaccines. Proteins incorporating rat sequences of IL-1RA, IL-2, IL-4, IL-10, or IL-13 were expressed as fusion proteins containing the major encephalitogenic region of myelin basic protein (MBP). These fusion proteins were expressed via baculovirus (bv) expression systems and were shown to have cytokine-dependent and antigen-specific biological activity. In the case of the IL-2 and IL-4 fusion proteins, covalent linkage of the cytokine and neuroantigen domains resulted in synergistic antigen presentation. These data indicate that the cytokine domain may be able to modulate APC activity and simultaneously target the covalently tethered NAg for enhanced presentation by certain APC subsets. Cytokine/antigen fusion proteins may represent a novel tool for antigen-specific immune modulation in autoimmune disease.
Mannie
Mark D
MD
The Department of Microbiology and Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27834, USA. manniem@ecu.edu
Devine
Jarret L
JL
Clayson
Barbara A
BA
Lewis
Leslie T
LT
Abbott
Derek J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D011993:Recombinant Fusion Proteins