TY - JOUR
T1 - Preferential T-cell receptor β-chain variable gene use in myelin basic protein-reactive T-cell clones from patients with multiple sclerosis
AU - Kotzin, Brian L.
AU - Karuturi, Satyanarayana
AU - Chou, Yuan K.
AU - Lafferty, Joyce
AU - Forrester, Joseph M.
AU - Better, Marc
AU - Nedwin, Glenn E.
AU - Offner, Halina
AU - Vandenbark, Arthur A.
PY - 1991/10/15
Y1 - 1991/10/15
N2 - Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. T cells specific for BP were cloned from the blood of multiple sclerosis patients and normal individuals, and expression of T-cell receptor variable region genes was analyzed. A remarkable bias for use of β-chain variable region (Vβ) 5.2 and, to a lesser extent, Vβ6.1 was seen among BP-specific clones from patients but not from controls. The preferential use of Vβ5.2 for BP recognition did not reflect altered expression of this Vβ in the peripheral repertoire. Interestingly, shared Vβ5.2 usage was apparent for clones specific for different BP determinants, even when derived from the same individual. The concurrent demonstration by others (J. R. Oksenberg, M. A. Panzara, A. B. Begovich, H. Erlich, R. Murray, M. Sherritt, S. Stuart, C. C. Bernard, and L. Steinman, personal communication) that T cells within demyelinating areas of multiple sclerosis brains preferentially express Vβ5.2 and Vβ6.1 suggests that the BP-specific clones derived from blood may be relevant to disease pathogenesis. These findings may have important implications for the treatment of multiple sclerosis.
AB - Multiple sclerosis is an autoimmune disease in which T lymphocytes reactive to myelin basic protein (BP) could play a central role. T cells specific for BP were cloned from the blood of multiple sclerosis patients and normal individuals, and expression of T-cell receptor variable region genes was analyzed. A remarkable bias for use of β-chain variable region (Vβ) 5.2 and, to a lesser extent, Vβ6.1 was seen among BP-specific clones from patients but not from controls. The preferential use of Vβ5.2 for BP recognition did not reflect altered expression of this Vβ in the peripheral repertoire. Interestingly, shared Vβ5.2 usage was apparent for clones specific for different BP determinants, even when derived from the same individual. The concurrent demonstration by others (J. R. Oksenberg, M. A. Panzara, A. B. Begovich, H. Erlich, R. Murray, M. Sherritt, S. Stuart, C. C. Bernard, and L. Steinman, personal communication) that T cells within demyelinating areas of multiple sclerosis brains preferentially express Vβ5.2 and Vβ6.1 suggests that the BP-specific clones derived from blood may be relevant to disease pathogenesis. These findings may have important implications for the treatment of multiple sclerosis.
KW - Autoimmune disease
KW - T-cell receptor repertoire
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U2 - 10.1073/pnas.88.20.9161
DO - 10.1073/pnas.88.20.9161
M3 - Article
C2 - 1717998
AN - SCOPUS:0026042680
SN - 0027-8424
VL - 88
SP - 9161
EP - 9165
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 20
ER -