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- Nicholson, L B, et al.
(författare)
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Monoclonal antibodies to the human TSH receptor: epitope mapping and binding to the native receptor on the basolateral plasma membrane of thyroid follicular cells.
- 1996
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Ingår i: Journal of molecular endocrinology. - 0952-5041. ; 16:2, s. 159-70
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Tidskriftsartikel (refereegranskat)abstract
- We have characterized four murine monoclonal antibodies (mAbs) to the extracellular domain of the human TSH receptor (TSH-R.E), the target autoantigen of Graves' disease. Recombinant TSH-R.E used as immunogen, was produced in E. coli as a fusion protein with glutathione-S-transferase or in a baculovirus-insect cell system, as a non-fusion glycoprotein. To increase the epitope specificity of the mAbs, two different strains of mice (H-2(b) and H-2(d)) were immunized. The epitopes recognized by the mAbs were characterized by immunoblotting with various recombinant constructs of TSH-R.E and by binding to overlapping synthetic peptides of the receptor. The four IgG mAbs characterized recognized epitopes localized to different regions on the TSH-R.E; amino acids 22-35 (A1O and A11, both IgG2b from H-2(b) animals), amino acids 402-415 (A7, IgG2b from H-2(b) animals) and amino acids 147-228 (A9, IgG1 from H-2(d) animals). Immunolocalization studies showed that mAb A9 recognized TSH-R.E on unfixed cryostat sections, where binding was localized to the basolateral plasma membrane of thyroid follicular cells, suggesting that this antibody reacts with the native receptor on thyroid cells. The binding of the mAbs A7, A10 and A11 was also restricted to the basal surface of thyroid cells, but only after acetone fixation of the sections, implying that the epitopes recognized on the amino and carboxyl terminus of the extracellular region of the receptor are not accessible on the native molecule. None of the mAbs stimulated cyclic AMP responses in COS-7 cells transiently transfected with full-length functioning TSH-R.E, whilst weak inhibition of binding of radiolabelled TSH to porcine membranes in a radioreceptor assay was apparent with mAb A10 and A11, but only at high concentrations of IgG. The ability of mAb A9 to bind to the native receptor without stimulating activity or inhibition of TSH binding suggests that antibody can bind to the central region of the TSH-R.E without perturbing receptor function. The availability of mAbs that recognize epitopes on different regions of the extracellular domain of TSH-R will lead to a better understanding of the autoantigenic regions on TSH-R implicated in disease activity.
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| 2. |
- Chu, H.S., et al.
(författare)
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VLBI observations of the puzzling BL Lacertae object 0235+164
- 1996
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Ingår i: Astronomy and Astrophysics. - : Springer. - 0004-6361 .- 1432-0746. ; 307:1, s. 15-20
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Tidskriftsartikel (refereegranskat)abstract
- For over 20 years, many models have been proposed to explain the variability of AO0235+164. Among them, the most favorable has been micro-lensing. We have made a series of VLBI observations on this source in order to better understand its nature. The resultant maps indicate dramatic changes in the position angle of the jet between observations as well as a correlation between the intensity of the VLBI core and flux outbursts which occurred between the observing sessions. These characteristics, in conjunction with other arguments, suggest that the source variability is intrinsic, i.e. microlensing is of minor importance. We suggest two models: 1) a model in which the jet starts at a very small angle to the line of sight and then curves away to become about 6deg at about 1 mas from the core; and 2) a CME (Coronal Mass Ejection) model that also may explain the violent variability in intensity, polarization position angle, and jet direction in AO0235+164.
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