Priming characteristics of peptide mimotopes of carbohydrate antigens.
Priming characteristics of peptide mimotopes of carbohydrate antigens.
复制标题
碳水化合物抗原的肽模拟表位的引发特征。
DOI：
10.1016/s0264-410x(02)00703-x
复制
发表时间：
2003
期刊：
影响因子：
5.5
通讯作者：
Kieber-Emmons,Thomas
中科院分区：
文献类型：
--
作者：
Monzavi-Karbassi,Behjatolah;Shamloo,Shahram;Kieber-Emmons,Matthew;Jousheghany,Fariba;Luo,Ping;Lin,KaityY;Cunto-Amesty,Gina;Weiner,DavidB;Kieber-Emmons,Thomas
用碳水化合物抗原的肽模拟物免疫可以诱导功能性碳水化合物反应性抗体。在这里，我们研究了免疫特性的替代方法，在总理和加强战略，使用糖基化的HIV-1包膜蛋白和模型肿瘤相关的碳水化合物抗原。我们的研究结果表明，肽模拟表位无论是在DNA或载体缀合的格式可以诱导相当的IgM和IgG水平。肽致敏动物的碳水化合物加强不影响终点滴度，然而，加强介导稳定持久的碳水化合物反应性IgM应答，这是单独碳水化合物免疫无法实现的。在用DNA-或肽-缀合物致敏的动物中用碳水化合物加强，有利于诱导具有显性IgG 2a同种型的可检测IgG。免疫与HIV-1包膜糖蛋白的肽引发的动物诱导不同的IgG同种型谱与显性IgG 1抗体。我们观察到，肽致敏小鼠的HIV-1包膜糖蛋白免疫诱导交叉反应性细胞应答，如通过细胞因子分泌所检测到的，其在脾细胞刺激后产生IFN-γ，并且在体外刺激后产生针对重组牛痘病毒感染的细胞的CTL活性。用模拟表位进行DNA免疫，在表达盒中包含来自HIV-1包膜蛋白的T细胞表位，并与IL-12或GM-CSF编码质粒共同给药，激活对HIV-1包膜蛋白的细胞应答。
Immunization with peptide mimetics of carbohydrate antigens can induce functional carbohydrate-reactive antibodies. Here, we examine the immune characteristics of alternative approaches in prime and boost strategies using glycosylated HIV-1 envelope protein and model tumor associated carbohydrate antigens. Our results indicate that peptide mimotopes either in a DNA or carrier-conjugated format can induce comparable levels of IgM and IgG. Carbohydrate boosting of peptide-primed animals does not affect end-point titer, however, boosting mediates a stable long lasting carbohydrate reactive IgM response, not achievable by carbohydrate immunization alone. Boosting with carbohydrate in animals primed with DNA- or peptide-conjugate, facilitates the induction of detectable IgG with a dominant IgG2a isotype. Immunization with HIV-1 envelope glycoprotein of peptide-primed animals induces different IgG isotype profiles with a dominant IgG1 antibody. We observed that HIV-1 envelope glycoprotein immunization of peptide primed mice induces a cross-reactive cellular response, as detected by cytokine secretion, which lends to IFN-γ production upon splenocyte stimulation and CTL activity against recombinant vaccinia virus infected cells after in vitro stimulation. DNA immunization with mimotope, inclusion of a T-cell epitope from the HIV-1 envelope protein in the expression cassette and co-administration with IL-12 or GM-CSF encoding plasmids activate a cellular response to the HIV-1 envelope protein.