Lachmann P J, Strangeways L, Vyakarnam A, Evan G
Ciba Found Symp. 1986;119:25-57. doi: 10.1002/9780470513286.ch3.
The use of PPD (purified protein derivative of tuberculin) as a carrier has several significant advantages. It provides very powerful T cell help and it gives rise to virtually no antibody response against itself. This is particularly useful if it is intended to go on to make monoclonal antibodies, where the presence of a large amount of anti-carrier antibody is a nuisance! Furthermore, unlike most comparably powerful adjuvant systems, it can be used in man. PPD coupling has been used to raise antibodies to haptens and to raise T cell responses to tumour cells. It is here reported that small peptides coupled to PPD will give rise to good titres of anti-peptide antibody. For peptides that contain no cysteine, coupling has been achieved by attaching succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) to the alpha-amino group of the peptide and N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) to the PPD and allowing an uncleavable bond to form between them. Data on immunization with the leucotactic nonapeptide of the alpha chain of the complement component C3 and with some oncogene-related peptides have been obtained.
使用结核菌素纯蛋白衍生物(PPD)作为载体有几个显著优点。它能提供非常强大的T细胞辅助,并且几乎不会引发针对自身的抗体反应。如果打算进一步制备单克隆抗体,这一点尤其有用,因为大量抗载体抗体的存在会带来麻烦!此外,与大多数同等强大的佐剂系统不同,它可用于人体。PPD偶联已被用于产生针对半抗原的抗体以及引发针对肿瘤细胞的T细胞反应。据报道,与PPD偶联的小肽能产生高滴度的抗肽抗体。对于不含半胱氨酸的肽,通过将4-(N-马来酰亚胺甲基)环己烷-1-羧酸琥珀酰亚胺酯(SMCC)连接到肽的α-氨基上,并将N-琥珀酰亚胺基-3-(2-吡啶二硫基)丙酸酯(SPDP)连接到PPD上,然后让它们之间形成不可裂解的键来实现偶联。已获得关于用补体成分C3α链的趋化九肽和一些癌基因相关肽进行免疫的数据。