GENERATION OF PROTEIN-REACTIVE ANTIBODIES BY SHORT PEPTIDES IS AN EVENT OF HIGH-FREQUENCY - IMPLICATIONS FOR THE STRUCTURAL BASIS OF IMMUNE RECOGNITION
GENERATION OF PROTEIN-REACTIVE ANTIBODIES BY SHORT PEPTIDES IS AN EVENT OF HIGH-FREQUENCY - IMPLICATIONS FOR THE STRUCTURAL BASIS OF IMMUNE RECOGNITION
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DOI：
10.1073/pnas.80.16.4949
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
LERNER, RA
中科院分区：
文献类型：
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作者：
NIMAN, HL;HOUGHTEN, RA;LERNER, RA
化学合成的小肽可以诱导通常与完整蛋白质反应的抗体，而不管它们在折叠分子中的位置如何。这些发现是很难解释的实验和理论数据表明，在没有由折叠的蛋白质提供的力，在水溶液中的小肽不容易采取稳定的结构。为了使这两个发现合理化，人们普遍接受了一个随机模型，该模型表明溶液中肽的多种构象异构体诱导了一组抗体，其中一小部分抗体与折叠蛋白共有的构象反应。随着蛋白质反应性抗肽抗体生成的成功率的增长，这种随机模型已经变得不那么站得住脚。为了测试随机模型，使用[小鼠]单克隆抗肽抗体来估计小肽诱导与折叠蛋白质反应的抗体的频率。由3种蛋白质制备了针对6种化学合成肽的单克隆抗体。肽诱导蛋白质反应性抗体的频率比先前实验工作预期的高至少4个数量级，并且与通过计算溶液中肽构象异构体的可能数量所预测的结果大不相同。这些发现使得随机模型不太可能，并导致考虑其他模型。除了它们对产生高度特异性试剂的实际意义外，这些发现可能对蛋白质折叠问题具有重要意义。
Chemically synthesized small peptides can induce antibodies that often react with intact proteins regardless of their position in the folded molecule. These findings are difficult to explain in view of the experimental and theoretical data which suggest that in the absence of forces provided by the folded protein, small peptides in aqueous solution do not readily adopt stable structures. To rationalize the 2 findings, there has been general acceptance of a stochastic model which suggests that the multiple conformers of a peptide in solution induce sets of antibodies with a small percentage reactive with conformations shared by the folded protein. This stochastic model has become less tenable as the success rate for the generation of protein-reactive anti-peptide antibodies has grown. To test the stochastic model, [mouse] monoclonal anti-peptide antibodies were used to estimate the frequency with which small peptides induce antibodies that react with folded proteins. Monoclonal antibodies to 6 chemically synthesized peptides were made from 3 proteins. The frequency with which the peptides induce protein-reactive antibodies is at least 4 orders of magnitude greater than expected from previous experimental work and vastly different from what would be predicted by calculating the possible number of peptide conformers in solution. These findings make the stochastic model less likely and lead to consideration to other models. Aside from their practical significance for generation of highly specific reagents, these findings may have important implications for the protein folding problem.