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

Highly purified synthetic peptides representing portions of the 68-86 sequence of guinea pig (GP) myelin basic protein (GPMBP) were used to define the N- and C-termini of encephalitogenic determinants that cause experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Each peptide was tested for: (a) induction of EAE, (b)in vitro potentiation of EAE transfer activity by GPMBP-sensitized lymph node cells (LNC), (c) in vitro proliferation of GPMBP-sensitized LNC, and (d) in vitro proliferation of a GPMBP-reactive line of EAE-inducing T cells. In these bioassays, the general rank order of potency was: GPMBP greater than or equal to GP68-86 greater than or equal to GP72-86 greater than [G84]GP68-86 greater than or equal to GP68-84 much greater than GP75-85 greater than or equal to GP75-84 = virtually no activity. These results demonstrate that the encephalitogenic region is bounded by the 72-74 and 84-86 sequences. Further evidence presented herein indicates that the 75-84 sequence contains the primary antigenic features required for specific T cell recognition of the encephalitogenic region.
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PMID:The N- and C-terminal boundaries of myelin basic protein determinants required for encephalitogenic and proliferative responses of Lewis rat T cells. 168 42

Four highly purified synthetic peptides encompassing segments of the 68-86 region [for the numbering system used, see Eylar, E.H., Brostoff, S., Hashim, G., Caccam, J. & Burnett, P. (1971) J. Biol. Chem. 246, 5770-5784] of myelin basic protein (MBP), a region known to induce experimental allergic encephalomyelitis (EAE) in Lewis rats, were used to define and compare structure-function relationships between the primary structure of the 68-86 sequence and the three following biological activities: induction of EAE in Lewis rats, stimulation of T lymphocytes in vitro as measured by augmented cellular transfer of EAE to syngeneic recipients, and lymphocyte proliferation, as measured by [3]thymidine incorporation. Guinea pig (GP) MBP was approximately 60 or 1500 times more active than the GP68-84 (Y G S L P Q K S Q R S Q D E N; single-letter amino acid abbreviations) or the modified bovine (MB) 68-84 (Y G S L P Q K A Q R P Q D E N) peptides for induction of EAE, respectively. Furthermore, lymphocytes primed with either GPMBP, GP68-84, or MB68-84 crossreacted in vitro with either GPMBP, GP68-84, or MB68-84 for activation of lymphocyte transfer activity. In contrast, lymphocytes primed with either GP68-84 or MB68-84 exhibited antigen-specific proliferation in vitro exclusively in response to either GP or MB sequences, respectively. Neither GP75-84 (S Q R S Q D E N) nor GP75-86 (S Q R S Q D E N P V) induced EAE, activated lymphocytes for EAE transfer, or stimulated lymphocyte proliferation under conditions and doses tested. We conclude that (i) structurally distinct determinants, reflecting existence of functionally independent classes of antigen receptors, specify encephalitogenic and proliferative responses of primed lymphocytes and (ii) determinants for EAE induction, cellular transfer of EAE, and lymphocyte proliferation include amino acid residues in the 68-74 (Y G S L P Q K) sequence of GPMBP.
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PMID:Induction of experimental allergic encephalomyelitis in Lewis rats with purified synthetic peptides: delineation of antigenic determinants for encephalitogenicity, in vitro activation of cellular transfer, and proliferation of lymphocytes. 387 98