Hannum C H, Matis L A, Schwartz R H, Margoliash E
J Immunol. 1985 Nov;135(5):3314-22.
An analysis of the fine specificities of the primary and hyperimmune antibody responses of B10.A mice to pigeon cytochrome c showed that both were qualitatively very similar. Small amounts of antibody appeared to be directed against the regions of serine 15 and/or glutamic acid 44. The remaining antibodies (greater than 70%) bound to the same complex topographic determinant (including residues 3, 103, and 104) on the back surface of pigeon cytochrome c which had been found to dominate the rabbit antibody response to this protein, and to be involved in Ia-restricted T cell stimulation. The mouse antibodies reacted very poorly with fragmented forms of the immunogen or with tobacco hornworm moth cytochrome c, even though both of these antigens had been shown previously to strongly stimulate pigeon cytochrome c-primed T cells. The specificities of the primary IgG responses of seven other mouse strains were found to be very similar, but not identical, to that of B10.A mice. The cytochrome c-specific antibodies in the hyperimmune serum were shown to bind to determinants involving residues that vary between pigeon and mouse cytochromes c. Comparison of the binding of the antibodies to the immunogen and to the corresponding host protein enabled the calculation of the proportion of the overall binding energy contributed by the variant residues. This was as low as 19 to 35% for the primary response, rose to 25 to 46% for the hyperimmune mouse antibodies, and reached 40 to 63% for hyperimmune rabbit antibodies. The remaining energy of interaction (37 to 81%) was necessarily contributed by the surface of the protein surrounding the variant residues, which is the same for the immunogen and the host protein. These results illustrate the relatively subtle differences in binding affinities which can distinguish self from non-self recognition by antibody molecules.
对B10.A小鼠针对鸽细胞色素c的初次和超免疫抗体反应的精细特异性分析表明，两者在性质上非常相似。少量抗体似乎针对丝氨酸15和/或谷氨酸44区域。其余抗体（超过70%）与鸽细胞色素c背面相同的复杂拓扑决定簇（包括残基3、103和104）结合，该决定簇已被发现主导兔子对该蛋白质的抗体反应，并参与Ia限制的T细胞刺激。即使先前已证明这两种抗原都能强烈刺激经鸽细胞色素c致敏的T细胞，但小鼠抗体与免疫原的片段形式或烟草天蛾细胞色素c的反应非常差。发现其他七种小鼠品系的初次IgG反应特异性与B10.A小鼠非常相似，但不完全相同。超免疫血清中的细胞色素c特异性抗体显示与涉及鸽和小鼠细胞色素c之间不同残基的决定簇结合。比较抗体与免疫原和相应宿主蛋白的结合情况，可以计算出变异残基贡献的总结合能比例。初次反应时该比例低至19%至35%，超免疫小鼠抗体升至25%至46%，超免疫兔子抗体则达到40%至63%。相互作用的其余能量（37%至81%）必然由围绕变异残基的蛋白质表面贡献，免疫原和宿主蛋白的该表面是相同的。这些结果说明了结合亲和力中相对细微的差异，这些差异可以区分抗体分子对自身和非自身的识别。
