Preferential peptide specificity and HLA restriction of myelin basic protein-specific T cell clones derived from MS patients

Zhang, Jingwu; Chou, Chi-Hsin Jen; Hashim, George A.; Medaer, Robert; Raus, Jef

doi:10.1016/0008-8749(90)90197-y

Cited by 34 publications

(4 citation statements)

References 40 publications

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“…In agreement with previous studies [9,16, 241, we demonstrate herein that more than 75% of the MBP-specific T-cell lines tested are able to mediate a substantial cytolysis of autologous MBP-coated target cells. The cytotoxic activity of MS-derived T-cell lines is not significantly higher than that of NS-derived Tcell lines.…”

Section: Oh Of Total Reactive T Cell Linessupporting

confidence: 92%

Myelin basic protein–specific T lymphocytes in multiple sclerosis and controls: Precursor frequency, fine specificity, and cytotoxicity

Zhang

Medaer

Hashim

et al. 1992

Annals of Neurology

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137

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A panel of 90 myelin basic protein (MBP)-specific T-cell lines were derived from peripheral blood of eight patients with multiple sclerosis and four normal subjects. The precursor frequency of MBP-reactive T cells in peripheral blood mononuclear cells ranged from 10(-7) to 9 x 10(-7) (mean, 6.7 x 10(-7)) in the group of patients with multiple sclerosis and from 0.5 x 10(-7) to 9.8 x 10(-7) (mean, 5.6 x 10(-7)) in the control subjects. This difference between the two groups was not statistically significant (p greater than 0.1). These T-cell lines expressed exclusively CD3+CD4+CD8- phenotypes and were restricted predominantly by HLA-DR molecules. When tested with fragments and synthetic peptides of human MBP, these MBP-specific T-cell lines (45 lines for each group) displayed a limited heterogeneous pattern with a biased recognition to peptide 84-102 and the C-terminal peptide 149-171. The reactivity to the 84-102 region of MBP was associated with the HLA-DR2, DRw15 (DRw15,2) haplotype, whereas the recognition to peptide 149-171 did not correlate with a particular HLA-DR allele(s). Furthermore, the majority of T-cell lines (greater than 75%) were found to exhibit substantial cytotoxic activity against MBP-coated target cells, but showing no significant difference between these two groups. This MBP-dependent cytotoxicity was not associated with epitope specificities of the T-cell lines tested.

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Section: Oh Of Total Reactive T Cell Linessupporting

confidence: 92%

Myelin basic protein–specific T lymphocytes in multiple sclerosis and controls: Precursor frequency, fine specificity, and cytotoxicity

Zhang

Medaer

Hashim

et al. 1992

Annals of Neurology

Self Cite

137

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“…The biological importance of this MBP region was also suggested by Richert et al (1989), who showed that nine out of forty MBP-specific human CD4+ T cell clones recognized MBP residues 86 to 105. Also, Jingwu et al (1990) reported that four out of 17 T cell clones established from MS patients recognized residues 108 to 148, a region which encompasses the homology region with HCV-229E. Finally, it is important to note that Allegretta et al (1990) have isolated circulating T cells which recognize the MBP of multiple sclerosis patients, lending further support to the importance of such an autoimmune reaction in pathology.…”

Section: Discussionmentioning

confidence: 94%

Sequence analysis of human coronavirus 229E mRNAs 4 and 5: evidence for polymorphism and homology with myelin basic protein

et al. 1992

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Human coronaviruses (HCV) are important pathogens responsible for respiratory, gastrointestinal and possibly neurological disorders. To better understand the molecular biology of the prototype HCV-229E strain, the nucleotide sequence of the 5'-unique regions of mRNAs 4 and 5 were determined from cloned cDNAs. Sequence analysis of the cDNAs synthesized from mRNA 4 revealed a major difference with previously published results. However, polymerase chain reaction amplification of this region showed that the sequenced cDNAs were produced from minor RNA species, an indication of possible genetic polymorphism in this region of the viral genome. The mutated messenger RNA 4 contains two ORFs: (1) ORF4a consisting of 132 nucleotides which potentially encodes a 44-amino acid polypeptide of 4653 Da; this coding sequence is preceded by a consensus transcriptional initiation sequence, CUAAACU, similar to the ones found upstream of the N and M genes; (2) ORF4b of 249 nucleotides potentially encoding an 83-amino acid basic and leucine-rich polypeptide of 9550 Da. On the other hand, mRNA 5 contains one single ORF of 231 nucleotides which could encode a 77-amino acid basic and leucine-rich polypeptide of 9046 Da. This putative protein presents a significant degree of amino acid homology (33%) with its counterpart found in transmissible gastroenteritis coronavirus (TGEV). The proteins in the two different viruses exhibit similar molecular weights and are extremely hydrophobic. Interestingly, a sequence homology of five amino acids was found between the protein encoded by ORF4b of HCV-229E and an immunologically important region of human myelin basic protein.

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“…Cette région conservée est associée à des sites encéphalitogènes de la PBM identifiés après l'injection des peptides correspondants à des animaux de laboratoire [30,34]. Elle se trouve à quelques résidus en aval de la région reconnue préférentiellement par le système immunitaire de patients atteints de SEP [31], et est la cible de lymphocytes retrouvés chez certains de ces patients [35,36]. Enfin, on peut signaler que la susceptibilité des cel lules nerveuses à 1' infection coronavirale in vitro a déjà été rappor tée pour un sérotype [37].…”

Section: Le Potentiel Neurotrope Des Coronavirusunclassified

“…Homologie entre une protéine virale et la protéine maje ure de la myéline. Une séquence de cinq aci des aminés d'une protéine non structurale de la souche prototype 229E du corona virus humain se retrouve sur la protéine basique de la myéline (PBM), près d'un site immunodominant reconnu par des lymphocytes de personnes atteintes de sclérose en plaques (SEP) [3 1 ], en aval ou dans le cadre de deux régions vues par des lymphocytes de certains de ces patients[35,36], et associée à des sites encépha/itogènes pour la souris[30], le rat [341 et le cobaye[30]. (D 'après[33].…”

unclassified

Le potentiel neurotrope des coronavirus

Talbot¹,

Jouvenne²

1992

Med Sci (Paris)

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Preferential peptide specificity and HLA restriction of myelin basic protein-specific T cell clones derived from MS patients

Cited by 34 publications

References 40 publications

Myelin basic protein–specific T lymphocytes in multiple sclerosis and controls: Precursor frequency, fine specificity, and cytotoxicity

Myelin basic protein–specific T lymphocytes in multiple sclerosis and controls: Precursor frequency, fine specificity, and cytotoxicity

Sequence analysis of human coronavirus 229E mRNAs 4 and 5: evidence for polymorphism and homology with myelin basic protein

Le potentiel neurotrope des coronavirus

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