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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/3929

Title: SPECIFICITY OF HUMAN T-CELL CLONES REACTIVE TO IMMUNODOMINANT EPITOPES OF MYELIN BASIC-PROTEIN
Authors: CHOU, YK
HENDERIKX, P
VAINIENE, M
WHITHAM, R
BOURDETTE, D
CHOU, CHJ
HASHIM, G
OFFNER, H
VANDENBARK, AA
Issue Date: 1991
Publisher: WILEY-LISS
Citation: JOURNAL OF NEUROSCIENCE RESEARCH, 28(2). p. 280-290
Abstract: Several recently discovered lines of evidence support the involvement of myelin basic protein (BP)-specific T cells in multiple sclerosis (MS). To identify potentially relevant immunodominant T cell epitopes, human BP (Hu-BP)-reactive T cell lines were selected from MS and normal donors and tested for reactivity to cleavage fragments and synthetic peptides of Hu-BP. The MS T cell lines responded to more Hu-BP epitopes than did normal lines, showing biased recognition of the N terminal half of the molecule, and one region in the C terminal half, suggesting increased sensitization to BP. The MS lines also differed from normal lines in their decreased percentage of CD8+ T cells. One hundred nine T cell clones isolated from these lines confirmed the reactivity pattern of the lines but did not reflect the mixed phenotype, since all but three clones tested were CD4+. T cell clones from HLA-DR2 homozygous donors responded to a variety of epitopes, indicating that this molecule was permissive in its ability to restrict T cell responses. Other epitopes, including the immunodominant 149-170 sequence, were restricted by several different major histocompatibility complex (MHC) molecules from both MS and normal donors. T cell receptor (TCR) V gene products could be identified on six of 38 clones tested using monoclonal antibodies. From one HLA-DR2 homozygous donor, four of eight clones utilized V-beta-5.2 in response to different BP epitopes, providing initial support for the preferential use of a limited set of V region genes in the human response to BP. Preferential TCR V gene use in MS patients would provide the rationale to regulate selectively BP-reactive T cells through immunity directed at the TCR and thus test for the first time the hypothesis that BP-reactive T cells play a critical role in the pathogenesis of MS.
Notes: OREGON HLTH SCI UNIV,DEPT NEUROL,PORTLAND,OR 97201. OREGON HLTH SCI UNIV,DEPT MICROBIOL & IMMUNOL,PORTLAND,OR 97201. DR L WILLEMS INST,DEPT IMMUNOL,DIEPENBEEK,BELGIUM. INST PSYCHIAT & NEUROL,WARSAW,POLAND. COLUMBIA UNIV,NEW YORK,NY 10027. EMORY UNIV,DEPT NEUROL,ATLANTA,GA 30322. ST LUKES ROOSEVELT HOSP,DEPT MICROBIOL & SURG,NEW YORK,NY 10025.CHOU, YK, OREGON HLTH SCI UNIV,VET AFFAIRS MED CTR,DEPT NEUROIMMUNOL RES,151D,PORTLAND,OR 97201.
URI: http://hdl.handle.net/1942/3929
DOI: 10.1002/jnr.490280215
ISI #: A1991FA37700014
ISSN: 0360-4012
Type: Journal Contribution
Appears in Collections: Non-affiliated authors

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