Aston R, Rathjen D A, Holder A T, Bender V, Trigg T E, Cowan K, Edwards J A, Cowden W B
Molecular Biology Laboratory, CSIRO Division of Biotechnology, Sydney, Australia.
Mol Immunol. 1991 Jan-Feb;28(1-2):41-50. doi: 10.1016/0161-5890(91)90085-x.
Site-directed antisera generated by peptide immunization have been used to study the antigenicity of bovine growth hormone (bGH). Prediction of sequential antigenic sites has been performed using secondary structure information derived from the 'Protean' prediction routine. The structures predicted by this programme agree closely with the corresponding structure of GH recently derived from crystallographic studies. We have previously shown that the binding of monoclonal antibodies of particular epitope specificity to human or bovine GH results in significant enhancement of hormonal activity in vivo; however, the sites recognized by these antibodies were not known. Here we identify a sequence region, corresponding to a loop structure joining helices 3 and 4, which, is associated with the growth enhancement phenomenon. Antisera raised to either of two overlapping peptides (residues 120-140 and 134-154) significantly increase the biological activity of GH in vivo. Antisera directed to other regions on the GH molecule failed to demonstrate this property. Coincidentally, the sites recognized by the growth-enhancing anti-peptide antisera overlap with the site on GH which is highly susceptible to proteolytic cleavage; such cleavage has been shown in some cases to result in hormone enhancement.
通过肽免疫产生的位点定向抗血清已被用于研究牛生长激素（bGH）的抗原性。利用从“Protean”预测程序获得的二级结构信息进行了连续抗原位点的预测。该程序预测的结构与最近通过晶体学研究得出的生长激素相应结构非常吻合。我们之前已经表明，具有特定表位特异性的单克隆抗体与人或牛生长激素的结合会在体内显著增强激素活性；然而，这些抗体识别的位点尚不清楚。在此，我们确定了一个与连接螺旋3和螺旋4的环结构相对应的序列区域，该区域与生长增强现象相关。针对两个重叠肽（残基120 - 140和134 - 154）之一产生的抗血清在体内显著提高了生长激素的生物活性。针对生长激素分子其他区域的抗血清未能显示出这种特性。巧合的是，生长增强抗肽抗血清识别的位点与生长激素上极易受到蛋白水解切割的位点重叠；在某些情况下，这种切割已被证明会导致激素活性增强。
