Multiple sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral encephalomyelitis and because of the presence in the blood of multiple sclerosis patients of in vivo-activated T cells reactive to myelin basic protein. Immune involvement in multiple sclerosis has been further suggested by the association with the major histocompatibility complex class II phenotype DR2, DQw1. To define the T-cell specificity toward myelin basic protein, 15,824 short-term T-cell lines were established from multiple sclerosis subjects, subjects with other neurological diseases, and normal controls. Here we report a higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84-102 in patients with multiple sclerosis compared with controls. A second region, identified between residues 143-168, was recognized equally in multiple sclerosis patients and controls and was associated with the DRw11 phenotype. These DR2 and DRw11 associations were also observed among T-cell lines generated from family members of a multiple sclerosis patient. The immunodominant 84-102 peptide from myelin basic protein was both DR2- and DQw1-restricted among different T-cell lines. These results raise the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals.

Multiple sclerosis (MS) may be an autoimmune disease mediated by T cells specific for a myelin protein. Investigations have demonstrated myelin basic protein (MBP)-reactive T cells that were activated in vivo in MS patients, suggesting that MBP may be a target antigen in MS. The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168). V beta 17 and to a lesser extent V beta 12 were frequently used in recognition of MBP(84-102) among different individuals. In contrast, V beta 17 was very infrequent among lines reactive with MBP (143-168). These data demonstrate shared TCR V beta gene usage for the recognition of immunodominant regions of the human autoantigen MBP. Such TCR structures may be used as targets for specific immunotherapy in MS.

Internal friction, torsional creep, and shear modulus relaxation experiments were conducted on a model Si3N4 polycrystalline material, which contained a continuous amorphous film of pure SiO2 at the grain boundary. Internal friction experiments were performed in the frequency range between 3 and 13 Hz, in 5 Pa of nitrogen atmosphere. Very high temperatures (up to 2000°C) could be applied for the first time by using a newly developed torsional pendulum apparatus. This apparatus was also capable of precise torsional strain measurements under static‐load conditions. The internal friction curves at various frequencies were generally found to consist of a grain‐boundary peak super‐imposed on an exponential‐like background. The peak, of anelastic diffusive origin, was centered in the temperature range of 1612–1710°C depending on the frequency of the measurement, namely within an interval of about 100°C below the nominal melting point of the pure SiO2 phase (i.e., ∼ 1730°C). The background was instead found to be of viscoelastic nature. A common micromechanical origin between the creep plastic strain and the internal friction background curves was identified and the data could be fitted by the same Arrhenius plot. Structural and chemical characterization of internal grain boundaries was performed by high‐resolution electron microscopy (HREM) in addition to electron energy‐loss spectroscopy (EELS). A small amount of nitrogen was detected within the amorphous residue along grain boundaries. According to the above set of microstructural/chemical and mechanical data, the viscosity properties of the intergranular phase were assessed and the sliding mechanism between adjacent Si3N4 grains was modeled.