Sequence determinants of modified cobra venom neurotoxin which induce immune resistance to experimental allergic encephalomyelitis: molecular mechanisms for immunologic action.
A nontoxic, iodoacetamide-modified cobratoxin derivative (CAM-NTX) induced resistance to experimental allergic encephalomyelitis (EAE) in guinea pigs. Resistance was retained after trypsin digestion and shown to reside in N-terminal and central peptides of CAM-NTX. A similarly modified protein cardiotoxin (CAM-CTX), representative of proteins homologous with cobratoxin, was not immunosuppressive. Depressed clinical symptoms in EAE-resistant animals correlated with reduced lymphocytic infiltration of the brain. Antibody to myelin basic protein (MBP) was reduced in immunosuppressed animals. The immunoinhibitory determinants in CAM-NTX may mimic immune response suppressor proteins (SIRS-alpha 7) and the EAE-resistance region of MBP.
Hinman
C L
CL
Department of Medicinal and Biological Chemistry, University of Toledo, Ohio 43606, USA.
Stevens-Truss
R
R
Schwarz
C
C
Hudson
R A
RA
D000595:Amino Acid Sequence; D000818:Animals; D004546:Elapid Venoms / Q000737:chemistry / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control*; D006168:Guinea Pigs; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004546:Elapid Venoms; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein; D009498:Neurotoxins