King T P, Kochoumian L, Chiorazzi N
J Exp Med. 1979 Feb 1;149(2):424-35. doi: 10.1084/jem.149.2.424.
The major allergen of ragweed pollen, antigen E, was modified by coupling its amino acid groups with either methanol, methoxypolyethylene glycol (MPEG) of 5,000 daltons, or a synthetic copolymer of D-glutamic acid and D-lysine (DGL) of 34,000 daltons, all appropriately activated. The conjugates were characterized chemically and immunologically. Compared to the native antigen, the methoxy conjugate showed little reduction in allergenic activity, but the other two conjugates showed strong reductions, as measured by heterologous passive cutaneous anaphylaxis in rats sensitized with murine anti-antigen E reaginic sera. The MPEG conjugate was apparently nonimmunogenic in mice known to be high responders to the native antigen. MPEG and DGL conjugates retained the immunosuppressive property of the native antigen as subcutaneous treatment of antigen E sensitized mice with these two conjugates led to significant long-lasting depression of their antigen E-specific IgE and IgG antibody levels. These immunological changes are believed to result from reduction of antigenic valency and specificity upon coupling the bulky molecules to the protein antigens.
豚草花粉的主要变应原——抗原E,通过将其氨基酸基团与甲醇、5000道尔顿的甲氧基聚乙二醇(MPEG)或34000道尔顿的D - 谷氨酸和D - 赖氨酸合成共聚物(DGL)进行偶联来进行修饰,所有这些均经过适当活化。对这些偶联物进行了化学和免疫学表征。与天然抗原相比,甲氧基偶联物的变应原活性降低很少,但通过用鼠抗抗原E反应素血清致敏的大鼠进行的异种被动皮肤过敏反应测定,另外两种偶联物的变应原活性显著降低。已知对天然抗原反应强烈的小鼠中,MPEG偶联物显然无免疫原性。MPEG和DGL偶联物保留了天然抗原的免疫抑制特性,因为用这两种偶联物皮下处理抗原E致敏的小鼠会导致其抗原E特异性IgE和IgG抗体水平显著且持久地降低。据信这些免疫变化是由于将大分子与蛋白质抗原偶联后抗原价和特异性降低所致。