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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/3927

Title: RESTRICTED T-CELL RECEPTOR-V-BETA GENE USAGE BY MYELIN BASIC PROTEIN-SPECIFIC T-CELL CLONES IN MULTIPLE-SCLEROSIS - PREDOMINANT GENES VARY IN INDIVIDUALS
Authors: Bennun, A.
Liblau, R.S.
Cohen, L.
Lehmann, D.
Tournierlasserve, E.
Rosenzwieg, A.
Zhang, J.K.
Raus, Jef
Bach, M.A.
Issue Date: 1991
Publisher: NATL ACAD SCIENCES
Citation: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 88(6). p. 2466-2470
Abstract: Recent studies in experimental autoimmune encephalomyelitis as a model for multiple sclerosis (MS) have demonstrated limited heterogeneity in T-cell antigen receptors (TCR) specific for myelin basic protein (MBP). To investigate restricted beta-chain variable-region (V-beta) gene usage in humans, we analyzed TCR gene rearrangements in two lines and 34 MBP-specific T-cell clones that were isolated from five MS patients and two healthy subjects. The T cells were characterized for their specificity to MBP epitopes and HLA-restricting molecules. We demonstrate here that MBP-specific T-cell clones from these different MS patients and healthy individuals, in contrast to T cells from rodents, display a more diverse V-beta gene usage as evidenced by their TCR V-beta gene rearrangements. However, the different MBP-specific T-cell clones isolated from each individual MS patient showed a common V-beta gene usage, suggesting individual-specific TCR restriction. Out of 16 MBP-specific clones derived from a single MS patient, 12 clones (75%) utilized the V-beta-15 gene for their TCR gene rearrangement. MBP-specific clones isolated from four other MS patients also showed a consistent tendency for a predominant, but different, TCR V-beta gene rearrangement. These results suggest a TCR heterogeneity among MBP-specific T-cell clones from different individuals but a limited TCR V-beta gene usage among MBP-specific T-cell clones of the same individual. The predominant V-beta gene used by the MBP-specific T-cell clones studied here was not found to correlate with the epitope specificity of T cells or with their restricting HLA molecule. These findings may support the possibility of intervention with monoclonal antibodies to specific V-beta gene products as an approach to immune therapy of MS but also imply the necessity for an individual-specific immunotherapeutic approach.
Notes: INST PASTEUR,UNITE PATHOL IMMUNITE,F-75724 PARIS 15,FRANCE. DR L WILLEMS INST,DEPT IMMUNOL,DIEPENBEEK,BELGIUM. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115.BENNUN, A, WEIZMANN INST SCI,DEPT CELL BIOL,IL-76100 REHOVOT,ISRAEL.
URI: http://hdl.handle.net/1942/3927
Link to publication: http://www.pnas.org/cgi/content/abstract/88/6/2466
ISI #: A1991FC21600091
ISSN: 0027-8424
Type: Journal Contribution
Appears in Collections: Research publications

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