The polyclonal antibody responses of Lewis rats to the synthetic encephalitogenic neuropeptide S55S (residues 72-84 of guinea pig myelin basic protein) and its analogs.
Immunochemical analysis of polyclonal antisera from Lewis rats immunized with peptide analogs and subpeptides of residues 72-84 of guinea pig myelin basic protein (MBP) indicated that there were four main epitopic specificities involved: one represented by residues 76-80, one by residues 72-74, one by 81-84-Gly, and one involving 74-76 in a heteroclitic way even when the immunogen contained a tetraleucine spacer between residues 74 and 75. The affinities were all relatively low, ranging from 3 x 10(4) M-1 to 7.2 x 10(6) M-1, and each affinity population was very restricted with respect to heterogeneity. The results were commensurate with our hypothesis that autoimmune responses to homologous encephalitogenic neuropeptide determinants reflect an evolutionarily imposed degeneration of the overall response, and were also in agreement with our hypothesis that the affinities of autoantibodies against epitopes in the molecular neighborhood of an encephalitogen would be necessarily low. It was also found that peptide 69-81-Gly (S67) in solution would not interact in liquid phase radioimmunoassays with any of the above antibody populations, thus indicating that its preferred conformation did not allow the expression of autoreactive epitopes. There was no evidence that S67 in solution. even in the presence of S53, would express any epitopes reactive with autoantibodies. How this finding for a B cell product correlates with T cell-mediated immunologic responses is not totally understood, but it will be recalled that S67 by itself does not induce T cell-mediated experimental allergic encephalomyelitis (EAE), that S53 (residues 75-84-Gly) induces only clinical symptoms of EAE without attendant pathological disease, but that the two together induce classical EAE.(ABSTRACT TRUNCATED AT 250 WORDS)
D000595:Amino Acid Sequence; D000818:Animals; D000937:Antigen-Antibody Reactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006168:Guinea Pigs; D004676:Myelin Basic Protein / Q000032:analysis / Q000276:immunology*; D009479:Neuropeptides / Q000032:analysis / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew
D004676:Myelin Basic Protein; D009479:Neuropeptides