ISSN:
0730-2312
Keywords:
anti-idiotypic antibodies
;
thyrotropin subunits
;
thyrotropin receptor
;
monoclonal antibody
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
TSH is a heterodimeric glycoprotein hormone, whose dissociated subunits are without biological activity. This has precluded the assessment of the relative contribution of each subunit to hormone action. We have raised anti-idiotypes to monoclonal antibodies specific, respectively, for the α and β hTSH subunits. The anti-β anti-idiotype inhibited l25I-hTSH binding to the β subunit-specific monoclonal quantitatively, whereas 125I-hTSH binding to the α subunit-specific monoclonal was not inhibited by anti-α anti-idiotypes, suggesting that only the former is an “internal image” anti-idiotype. Neither of the two anti-idiotypes nor equimolar mixtures thereof inhibited 125I-bTSH binding to thyroid membranes, even though radiolabelled anti-idiotypes showed saturable binding to thyroid plasma membrane which was inhibited 41-65% by bTSH. Each anti-idiotype alone caused 9% inhibition (compared to 50% by NRIgG) of thyroid plasma membrane adenylate cyclase. Equimolar mixtures (125 μg/ml IgG of each anti-idiotype) induced enzyme activity equivalent to 85% of that of 250 mU/ml of TSH. The TSH-like action of the two anti-idiotypes was also reflected in their capacity to increase (450% by 250 μg/ml IgG compared to normal rabbit IgG) the uptake of 131I into isolated thyrocytes and to promote the organization of such cells into follicular structures. At 250 μg/ml, anti-β anti-idiotype promoted the organization of small follicles and only at a concentration of 500 μg/ml did it enhance 131I uptake. Anti α idiotype was without effect in both assays. Lastly, mixture of anti-idiotypes bound to the ∼ 197,000 Mr band (TSH holoreceptor) on protein blots of thyroid plasma membranes resolved on NaDSO4-polyacrylamide gel electrophoresis under non-reducing conditions. Individual anti-idiotypes were without effect.The TSH α and β subunits apparently deliver two cooperative signals to the receptor and that specificity is associated with the β subunit, while the α subunit is important in enhancing receptor affinity for the heterodimer and in stablizing TSH-receptor complex.
Additional Material:
6 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240340302
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