Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Region 65-102 of the myelin basic protein (MBP) houses a number of antigenic determinants known to induce delayed-type hypersensitivity, experimental allergic encephalomyelitis (EAE), suppressor cell function, and antibodies. In this report we describe the biological activity of synthetic peptides S53, S55, and S49 with sequence homology to region 69-84 of the rat, guinea pig, and bovine MBP. Peptide S53-A, defined by residues 75-84 of the guinea pig (SQRSQDEN) and of the rat (SQRTQDEN) MBP induced clinical signs of disease in Lewis rats. These included weight loss, flaccid tail, "muscle wasting," and hind-leg weakness. Histological examination of brain, spinal cord, and sciatic nerve sections of diseased rats revealed the complete absence of focal and perivascular lymphocytic infiltrates characteristics of demyelinating EAE lesions. Elongation of peptide S53 by three or six residues to residue sequences naturally found at its N-terminal end gave rise to peptides S55S (PQKSQRSQDEN) and S49S (GSLPQKSQRSDQDEN), respectively. Lewis rats challenged with either S55S or S49S developed classical clinical and histological signs of EAE. Severe hind-leg paralysis was accompanied by incontinence and sometimes death. Injected in the form of carrier-free peptide, S53 was a meager B cell immunogen. S53 conjugated with methylated-bovine serum albumin was also a potent immunogen and produced clinical signs of disease without CNS pathology. By comparison, carrier-free S55S and S49S were potent immunogens giving rise to antibodies that cross reacted completely and competitively with S55S but considerably less so with S53. The results show that the sequence of S53 defines an epitope responsible for the formation of anti-S53 antibodies. Elongation of the S53 sequence at its N-terminal end generated an additional epitope which induced cell-mediated immunity responsible for the concomitant development of pathological signs of EAE. It may be concluded that the induction of classical signs of EAE requires specific and defined sequences capable of expressing both B cell and T cell functions.
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PMID:Biological activity of region 65-102 of the myelin basic protein. 243 Jan 4

Studies from our laboratory have shown that classical clinical and histological signs of experimental allergic encephalomyelitis (EAE) may be induced in Lewis rats by synthetic peptides S49 or S55. Peptides S49S and S55S are defined by residues 69-84 and 72-84 of the guinea pig myelin basic protein (MBP), respectively. Peptide S53 (residues 75-84 of the guinea pig MBP), six residues shorter than S49S at the N-terminal end, induced mild clinical signs of disease unaccompanied by hind leg paralysis, incontinence, or central nervous system pathology. In contrast, peptide S67 (residues 69-81 of the guinea pig MBP), three residues shorter than S49S at the C-terminal end, did not induce either clinical or histological signs of EAE despite the fact that the S67-sequence houses an epitope known to induce cell-mediated immunity. Peptides S49S, S55S, and S53 are antigenic and gave rise to antibodies that recognized either of the three peptide sequences. In this report we explore the interrelationship between cellular immunity induced by the S67 sequence and humoral immunity, induced by the S53 sequence and the development of classical clinical and histological signs of EAE. The results show that the nonencephalitogenic sequence of S67 may be rendered encephalitogenic in the presence of antibody directed against the S53 sequence. Lewis rats immunized with S53 developed pathological signs of EAE only after they were challenged with S67. The fact that a simultaneous challenge with S67 and S53 was as effective in inducing EAE pathology as a delayed one (up to 40 days) suggests that the cellular response to S67 is dependent upon the humoral response to S53.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental allergic encephalomyelitis (EAE): role of B cell and T cell epitopes in the development of EAE in Lewis rats. 244 6

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)
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PMID: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. 244 1