Use of anti-idiotypic antibodies as probes for the interaction of TSH subunits with its receptor

✍ Scribed by Rosario Briones-Urbina; M. N. Islam; J. Ivanyi; Nadir R. Farid

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 751 KB
• Volume: 34
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240340302

✦ Synopsis

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 01 and 0 hTSH subunits. The anti-0 anti-idiotype inhibited 1251-hTSH binding to the 0 subunit-specific monoclonal quantitatively, whereas '251-hTSH binding to the 01 subunit-specific monoclonal was not inhibited by anti-a 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 NlUgG) of thyroid plasma membrane adenylate cyclase. Equimolar mixtures (125 pg/ml IgG of each anti-idiotype) induced enzyme activity equivalent to 85% of that of 250 mU/ml of TSH. The TSHlike action of the two anti-idiotypes was also reflected in their capacity to increase (450% by 250 pglml IgG compared to normal rabbit IgG) the uptake of I3'I into isolated thyrocytes and to promote the organization of such cells into follicular structures. At 250 pg/ml, anti-0 anti-idiotype promoted the organization of small follicles and only at a concentration of 500 pg/ml did it enhance 13'1 uptake.

Abbreviations used: AC, adenylate cyclase; anti-id, anti-idiotype; 01 anti-id and (3 anti-id, antibodies raised against monoclonals specific for the 01 and (3 subunits, respectively, of TSH; bTSH, bovine thyrotropin; DEAE, diethylamino ethyl; FCS, fetal calf serum; FSH, follicle stimulating hormone; HAT,