Gleason S L, Gearhart P, Rose N R, Kuppers R C
Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205.
J Immunol. 1990 Sep 15;145(6):1768-75.
Murine experimental autoimmune thyroiditis has been used as a model for human autoimmune thyroiditis. Experimental autoimmune thyroiditis is induced in mice by immunization with mouse thyroglobulin (Tg) in CFA. To characterize the antibodies to this autoantigen, we have studied the binding specificities and determined the nucleotide sequences of monoclonal anti-Tg antibodies. The specificities of the mAb for determinants on Tg varied extensively. Seven of 16 mAb showed reactivity to only mTg, 4 reacted to Tg from more than one species and four reacted to a variety of Ag. Many of the mAb were competitively inhibited by thyroid hormones, suggesting that they recognize the hormonogenic sites on the Tg molecule. The mAb could be divided into at least seven reactivity patterns based on reciprocal competitive inhibition studies, indicating that mTg contains at least seven antigenic regions. DNA sequence analysis of the mAb showed that a large number of V region gene segments encoded the H and L chains. No evidence for preferential use of any V region family or gene segment was found. Gene segments from the VH 7183, Q52, J558, and VH10 families were used by heavy chains, and the V kappa 1, 4, 8, 9, 19, and 21 families were used by kappa-chains. The results indicate that the antigenic epitopes on mTg elicit a very diverse autoantibody response that is derived from a large number of V region gene segments. Many of these autoantibodies show specific reactivity with mTg indicating they recognize species specific epitopes. The results suggest that clonal deletion of autoreactive Ab to certain self-epitopes may not occur.
小鼠实验性自身免疫性甲状腺炎已被用作人类自身免疫性甲状腺炎的模型。通过在弗氏完全佐剂（CFA）中用小鼠甲状腺球蛋白（Tg）免疫来诱导小鼠发生实验性自身免疫性甲状腺炎。为了表征针对这种自身抗原的抗体，我们研究了结合特异性并确定了单克隆抗Tg抗体的核苷酸序列。单克隆抗体（mAb）对Tg上决定簇的特异性差异很大。16种mAb中有7种仅对小鼠Tg有反应，4种对来自多个物种的Tg有反应，4种对多种抗原（Ag）有反应。许多mAb被甲状腺激素竞争性抑制，这表明它们识别Tg分子上的激素生成位点。基于相互竞争抑制研究，mAb可分为至少七种反应模式，这表明小鼠Tg至少包含七个抗原区域。对mAb的DNA序列分析表明，大量的V区基因片段编码重链和轻链。未发现优先使用任何V区家族或基因片段的证据。重链使用来自VH 7183、Q52、J558和VH10家族的基因片段，κ链使用Vκ1、4、8、9、19和21家族的基因片段。结果表明，小鼠Tg上的抗原表位引发了非常多样化的自身抗体反应，该反应源自大量的V区基因片段。这些自身抗体中有许多对小鼠Tg表现出特异性反应，表明它们识别物种特异性表位。结果表明，针对某些自身表位的自身反应性抗体的克隆清除可能不会发生。
