Restricted T-cell receptor V beta gene usage by myelin basic protein-specific T-cell clones in multiple sclerosis: predominant genes vary in individuals.
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.
Ben-Nun
A
A
Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Liblau
R S
RS
Cohen
L
L
Lehmann
D
D
Tournier-Lasserve
E
E
Rosenzweig
A
A
Zhang
J W
JW
Raus
J C
JC
Bach
M A
MA
D001483:Base Sequence; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D004676:Myelin Basic Protein / Q000235:genetics* / Q000276:immunology; D015345:Oligonucleotide Probes; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D004676:Myelin Basic Protein; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell