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)

Experimental allergic encephalomyelitis (EAE) serves as a model for autoimmune diseases mediated by T lymphocytes. Following sensitization to rat, mouse or guinea pig myelin basic protein (MBP) in complete Freund's adjuvant, inbred mouse strains PL/J (H-2u), SJL/J (H-2s) and (PL/J X SJL/J)F1((PLSJ)F1) develop EAE. Whereas sensitization to the N-terminal 37 amino-acid peptide of rat or guinea pig MBP [MBP(1-37)] induces EAE in PL/J mice, immunization to the C-terminal peptide (89-169) leads to EAE in SJL/J mice. The immune response to MBP in (PLSJ)F1 mice is not co-dominant; sensitization to the N-terminal peptide induces EAE, while sensitization to the C-terminal peptide does not. We have generated MBP-specific T-cell clones restricted to class II (Ia) antigens of the major histocompatibility complex (MHC) from PL/J and (PLSJ)F1 mice following sensitization to rat MBP. Two such I-Au-restricted T-cell clones that proliferate in response to the encephalitogenic N-terminal MBP peptide and recognize a shared determinant with mouse (self) MBP cause paralysis in 100% of (PLSJ)F1 mice tested. Paralysis is induced even when recipients are injected with as few as 1 X 10(5) cloned T cells. Relapsing paralysis followed in two-thirds of the recipients after recovery from acute paralysis, whereas one-third developed chronic persistent paralysis, a form of EAE not usually seen. Histopathology revealed intense perivascular inflammation, demyelination and remyelination within the central nervous system of paralysed mice. The experimental disease induced with these clones shares important features with human demyelinating diseases such as multiple sclerosis. This is the first demonstration that T-cell clones that respond to a defined self-antigen can induce clinical and histological autoimmune disease.
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PMID:T-cell clones specific for myelin basic protein induce chronic relapsing paralysis and demyelination. 241 63

Class II-restricted T cell clones specific for myelin basic protein (MBP) have been generated from PL/J and (PL/J X SJL/J)F1 [((PLSJ)F1] mice following sensitization to rat MBP. Of 17 T cell clones generated from (PLSJ)F1 mice, 5 are I-Au(A alpha uA beta u) restricted, one is restricted to I-As(A alpha sA beta s), 10 are restricted to hybrid I-A(u X s)F1 (A alpha sA beta u) determinants, and one clone is restricted to hybrid I-E(u X s) (E alpha uE beta s) molecules. Thus, of 16 I-A-restricted T cell clones generated from (PLSJ)F1 mice, only one is I-As-restricted, reflecting a lack of priming to MBP in association with I-As. T cell clones restricted to I-Au and to I-E (E alpha u E beta s) molecules recognize mouse (self) MBP. Furthermore, only the five T cell clones restricted to I-Au molecules recognize a determinant in common with mouse (self) MBP within the encephalitogenic N-terminal peptide. Three such I-Au restricted T cell clones, derived independently, cause paralysis in 100% of (PL/J X SJL/J)F1 mice tested. Acute, chronic unremitting, and chronic relapsing paralysis are all induced following injection of these clones. Administration of greater numbers of cloned T cells causes acute and fatal experimental allergic encephalomyelitis, while administration of lower numbers of cloned T cells is associated with chronic unremitting and relapsing paralysis. Paralysis induced with T cell clones shares many clinical, immunologic, and histologic aspects with human demyelinating diseases such as multiple sclerosis. Histopathology reveals perivascular lymphocytic infiltration, demyelination, and remyelination. These studies demonstrate the utility of T cell clones for analyzing the association between class II major histocompatibility complex molecules and disease susceptibility.
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PMID:Encephalitogenic T cell clones specific for myelin basic protein. An unusual bias in antigen recognition. 241 64

The C-terminal 89-169 amino acid fragment of myelin basic protein (MBP) causes experimental allergic encephalomyelitis (EAE) in SJL/J mice. In order to identify the encephalitogenic T cell epitope, we have examined the fine specificity of encephalitogenic SJL/J T cell clones with synthetic peptides derived from the C-terminal 89-169 amino acids of MBP. These peptides were examined for their immunogenic and encephalitogenic activity in the SJL/J mouse. The SJL/J-derived, encephalitogenic T cell clone, 4b.14a, was shown to be responsive to rat myelin basic protein synthetic peptides pR89-101 (VHFFKNIVTPRTP) as well as to intact MBP. Its response was effectively blocked by mAb 10-2.16 (anti-I-As) as was the response to intact MBP. Furthermore, pR89-101 was revealed to be highly immunogenic for the (PLSJ)F1 mouse in terms of lymphocyte proliferation, but not for the PL/J mouse, in spite of the fact that there exists a strong bias to H-2u restricted responses in the (PLSJ)F1 mouse at the T cell level. By using pR89-101, T cells of (PLSJ)F1 origin were revealed to recognize the peptide in association with the I-As molecule on (PLSJ)F1 antigen presenting cells (APC). When examined for encephalitogenicity for the SJL/J mouse, pR89-101 was found to be as encephalitogenic as intact rat MBP. These results demonstrated that MBP peptide pR89-101 is a major encephalitogenic determinant for the SJL/J mouse.
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PMID:Characterization of a major encephalitogenic T cell epitope in SJL/J mice with synthetic oligopeptides of myelin basic protein. 245 4