The effect of haptens on protein-carrier immunogenicity
The effect of haptens on protein-carrier immunogenicity
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DOI：
10.1111/imm.12356
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发表时间：
2015-01-01
期刊：
影响因子：
6.4
通讯作者：
Pitcovski, Jacob
中科院分区：
文献类型：
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作者：
Gefen, Tal;Vaya, Jacob;Pitcovski, Jacob
针对半抗原的免疫应答是T细胞依赖性的，因此需要抗原呈递细胞将MHC II类分子上的肽摄取、加工和呈递至特异性T细胞。一些半抗原在与载体蛋白表面上的可用游离胺缀合后可以降低其免疫原性。本研究的目的是探索这种情况发生的机制。四种蛋白质作为载体进行了测试，六种分子被用作半抗原。对载体蛋白的免疫应答被一些半抗原降低>100倍（称为载体免疫原性降低半抗原-CIRH），而其他半抗原不影响蛋白免疫原性（载体免疫原性非降低半抗原-nCIRH）。蛋白质与CIRH的缀合影响溶酶体组织蛋白酶的蛋白质降解，导致产生的肽在长度和序列上与来自相同天然蛋白质或用nCIRH修饰的蛋白质的肽不同。将CIRH结合蛋白注射到小鼠中诱导调节性T细胞群体的增加。本研究的结果提供了一个假定的作用机制，为减少免疫反应的半抗原化蛋白。
The immune response against hapten is T-cell-dependent, and so requires the uptake, processing and presentation of peptides on MHC class II molecules by antigen-presenting cells to the specific T cell. Some haptens, following conjugation to the available free amines on the surface of the carrier protein, can reduce its immunogenicity. The purpose of this study was to explore the mechanism by which this occurs. Four proteins were tested as carriers and six molecules were used as haptens. The immune response to the carrier proteins was reduced >100-fold by some of the haptens (termed carrier immunogenicity reducing haptens-CIRH), whereas other haptens did not influence the protein immunogenicity (carrier immunogenicity non-reducing haptens-nCIRH). Conjugation of the protein to a CIRH affected protein degradation by lysosomal cathepsins, leading to the generation of peptides that differ in length and sequence from those derived from the same native protein or that protein modified with nCIRH. Injection of CIRH-conjugated protein into mice induced an increase in the population of regulatory T cells. The results of this study provide a putative mechanism of action for the reduction of immune response to haptenated proteins.