The influence of natural antibody specificity on antigen immunogenicity
The influence of natural antibody specificity on antigen immunogenicity
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DOI：
10.1002/eji.200526146
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Iacomini, J
中科院分区：
文献类型：
--
作者：
Benatuil, L;Kaye, J;Iacomini, J
人类、猿类和东半球灵长类动物的天然抗体库与所有其他胎盘哺乳动物的抗体库不同，它编码针对碳水化合物表位Galα1-3 Galβ1-4GlcNAc-R(Alpha Gal)的抗体。在这里，我们研究了α-半乳糖基转移酶基因敲除小鼠(GT(O)小鼠)的α(1，3)半乳糖基转移酶表位结合抗原是否能增强它们的免疫原性，而GT(O)小鼠和人类一样，产生α-Gal特异性抗体。用α-半乳糖结合的牛血清白蛋白(α-GalBSA)免疫GT(O)小鼠，可以在不需要佐剂的情况下产生大量的抗-BSA-Ig G抗体。这种反应依赖于α-半乳糖反应性抗体的存在。用α-Gal-BSA免疫野生型小鼠未能诱导抗BSA反应。与单独接受牛血清白蛋白免疫的小鼠相比，agal反应性抗体的存在也导致了免疫后T细胞对牛血清白蛋白的反应增加，导致产生干扰素-伽马和IL-4的牛血清白蛋白特异性T细胞的频率增加。此外，在免疫小鼠白血病病毒转化的细胞株后，产生αGal反应抗体的能力增强了细胞毒性T淋巴细胞抗病毒抗原的反应，这些细胞株在细胞表面表达αGal。因此，结合α-半乳糖的天然抗体在提高对修饰了α-半乳糖表位的抗原的启动效率方面起着关键作用。
The natural antibody repertoire in humans, apes and Old World primates is distinct from the repertoire of all other placental mammals, and encodes antibodies specific for the carbohydrate epitope Gal alpha 1-3 Gal beta 1-4GlcNAc-R (alpha Gal). Here, we examined whether conjugating antigens to the alpha Gal epitope can augment their immunogenicity in alpha(1,3)galactosyltransferase knockout mice (GT(o) mice) which, like humans, produce alpha Gal-specific antibodies. Immunization of GT(o) mice with BSA conjugated to alpha Gal (alpha GalBSA) led to significant production of anti-BSA IgG antibodies without the need for adjuvant. This response was dependent on the presence of alpha Gal-reactive antibodies. Immunization of wild-type mice with alpha Gal-BSA failed to induce an anti-BSA response. The presence of aGal-reactive antibodies also led to an increase in the T cell response to BSA following immunization with alpha Gal-BSA when compared with mice that received BSA alone, resulting in an increased frequency of IFN-gamma- and IL-4-producing BSA-specific T cells. In addition, the ability to produce alpha Gal-reactive antibodies enhanced the cytotoxic T lymphocyte anti-viral antigen response following vaccination with murine leukemia virus transformed cell lines that express alpha Gal on their cell surface. Natural antibodies that bind alpha Gal therefore play a key role in increasing the efficiency of priming to antigens decorated with alpha Gal epitopes.