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用卵清蛋白 - 单甲氧基聚乙二醇(OA - mPEG)偶联物脉冲处理的巨噬细胞诱导小鼠抗体应答的体内辅助活性。

Induction of in vivo helper activity for murine antibody responses by macrophages pulsed with ovalbumin-monomethoxypolyethylene glycol (OA-mPEG) conjugates.

作者信息

Holford-Strevens V, Jackson C J, Charlton J, Akiyama K A, Lang G M, Carter B G, Sehon A H

出版信息

Cell Immunol. 1987 Feb;104(2):245-54. doi: 10.1016/0008-8749(87)90027-x.

Abstract

Conjugates of protein antigens with an optimal number of monomethoxypolyethylene glycol (mPEG) chains of an appropriate molecular weight had been shown to suppress murine IgE responses to the unmodified antigen. To investigate the possibility that the tolerogenic capacity of these mPEG conjugates is attributable to a defect in macrophage (M phi) presentation of their antigenic determinants, the activity of ovalbumin (OA)-mPEG conjugates when pulsed onto mouse peritoneal adherent cells (M phi) was compared in this study with their activity in solution. Surprisingly, in contrast to the suppressogenic capacity of mPEG conjugates in solution, the OA-mPEG pulsed M phi appeared to exert a helper effect when injected intraperitoneally (ip), i.e., after subsequent immunization with dinitrophenylated OA (DNP3-OA) in Al(OH)3, the mice showed accelerated IgE and IgG1 antibody responses to OA and DNP. However, when M phi were exposed to limiting concentrations of OA or OA-mPEG, markedly higher concentrations of OA-mPEG were required to yield pulsed M phi, exerting a significant helper effect. It was concluded that although M phi were capable of presenting the OA determinants of OA-mPEG conjugates to helper T (Th) cells, the preparations of modified antigen were presented less effectively than native OA.

摘要

已证明,具有最佳数量且分子量合适的单甲氧基聚乙二醇(mPEG)链的蛋白质抗原缀合物可抑制小鼠对未修饰抗原的IgE反应。为了研究这些mPEG缀合物的致耐受性能力是否归因于巨噬细胞(M phi)呈递其抗原决定簇的缺陷,在本研究中,将卵清蛋白(OA)-mPEG缀合物脉冲到小鼠腹膜黏附细胞(M phi)上时的活性与其在溶液中的活性进行了比较。令人惊讶的是,与mPEG缀合物在溶液中的抑制能力相反,经OA-mPEG脉冲处理的M phi经腹腔注射(ip)后似乎发挥辅助作用,即在用氢氧化铝中的二硝基苯基化OA(DNP3-OA)进行后续免疫后,小鼠对OA和DNP的IgE和IgG1抗体反应加快。然而,当M phi暴露于有限浓度的OA或OA-mPEG时,产生具有显著辅助作用的脉冲M phi需要明显更高浓度的OA-mPEG。得出的结论是,尽管M phi能够将OA-mPEG缀合物的OA决定簇呈递给辅助性T(Th)细胞,但修饰抗原的制剂的呈递效果不如天然OA。

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