Antigen stability controls antigen presentation
Antigen stability controls antigen presentation
复制标题
DOI：
10.1074/jbc.m405738200
复制
发表时间：
2004-11-26
影响因子：
4.8
通讯作者：
Léonetti, M
中科院分区：
文献类型：
--
作者：
Thai, R;Moine, G;Léonetti, M
我们研究了蛋白质的稳定性是否控制抗原呈递使用四个含二硫键的蛇毒素和三个衍生物携带一个或两个突变（L1 A，L1 A/H4 Y和H4 Y）。预期这些突变会增加（H4 Y）或减少（L1 A）抗原非共价稳定相互作用，H4 Y在神经毒素中天然且经常观察到。化学合成的衍生物具有相似的三维结构、生物活性和T表位模式。然而，它们显示出不同的热去折叠能力，范围从65到98 ℃。使用这些差异稳定的衍生物，我们证明了抗原稳定性控制抗原蛋白水解，抗原呈递细胞中的抗原加工，T细胞刺激和T细胞决定簇表达的动力学。因此，控制抗原解折叠能力的非共价相互作用是抗原呈递功效的关键参数。通过影响蛋白质的稳定相互作用网络，一些自然突变可能会调节随后的T细胞刺激，并可能帮助微生物逃避免疫反应。
We investigated whether protein stability controls antigen presentation using a four disulfide-containing snake toxin and three derivatives carrying one or two mutations (L1A, L1A/H4Y, and H4Y). These mutations were anticipated to increase (H4Y) or decrease (L1A) the antigen non-covalent stabilizing interactions, H4Y being naturally and frequently observed in neurotoxins. The chemically synthesized derivatives shared similar three-dimensional structure, biological activity, and T epitope pattern. However, they displayed differential thermal unfolding capacities, ranging from 65 to 98degreesC. Using these differentially stable derivatives, we demonstrated that antigen stability controls antigen proteolysis, antigen processing in antigen-presenting cells, T cell stimulation, and kinetics of expression of T cell determinants. Therefore, non-covalent interactions that control the unfolding capacity of an antigen are key parameters in the efficacy of antigen presentation. By affecting the stabilizing interaction network of proteins, some natural mutations may modulate the subsequent T-cell stimulation and might help microorganisms to escape the immune response.