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Sökning: WFRF:(Davies C. T. H.) > (1995-1999) > Monoclonal antibodi...

  • Nicholson, L B (författare)

Monoclonal antibodies to the human TSH receptor: epitope mapping and binding to the native receptor on the basolateral plasma membrane of thyroid follicular cells.

  • Artikel/kapitelEngelska1996

Förlag, utgivningsår, omfång ...

  • 1996

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/280386
  • https://gup.ub.gu.se/publication/280386URI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Vlase, H (författare)
  • Graves, P (författare)
  • Nilsson, M (författare)
  • Mölne, Johan,1958Gothenburg University,Göteborgs universitet,Institutionen för laboratoriemedicin , Avdelningen för patologi,Institute of Laboratory Medicine, Dept of Pathology(Swepub:gu)xmolnj (författare)
  • Huang, G C (författare)
  • Morgenthaler, N G (författare)
  • Davies, T F (författare)
  • McGregor, A M (författare)
  • Banga, J P (författare)
  • Göteborgs universitetInstitutionen för laboratoriemedicin , Avdelningen för patologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of molecular endocrinology16:2, s. 159-700952-5041

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