Tomlinson L A, Christie J F, Fraser E M, McLaughlin D, McIntosh A E, Kennedy M W
Wellcome Laboratories for Experimental Parasitology, University of Glasgow, Scotland.
J Immunol. 1989 Oct 1;143(7):2349-56.
Humans vary considerably in the antigen specificity of their immune responses to parasitic nematodes, and in the infection loads of individuals living in the same environment. The possibility that the former has a genetic basis operating through repertoire control of the immune system was investigated using infection of mice with the nematode Ascaris. The specificity of the antibody response was examined using excretory/secretory (ES) materials of the parasite as target Ag. No strain of mouse was found to recognize all of the potentially antigenic components of ES, and the Ag recognition patterns varied considerably from strain to strain. Using H-2 congenic mice on both the BALB and B10 backgrounds, it was established that the antigen recognition patterns were MHC-determined. Focusing on one particular component of ES, of Mr 14,000, only H-2s strains responded in IgG. This MHC restriction of the repertoire was confined to infection, and broke down under adjuvant-assisted immunization with the purified protein. The Mr 14,000 molecule was also found to be a potent allergen in a passive cutaneous anaphylaxis assay, and the IgE response to it was also restricted to H-2s. This haplotype was, however, a low IgE responder on the SJL background. There is, therefore, MHC control of the specificity of the immune response to this molecule, but non-MHC control of the amplitude of the IgE antibody response to it. Hybrids between responder and nonresponder strains (BALB/c x SJL)F1, responded to the Mr 14,000, but their responses to other ES components could not be predicted from the response patterns of parental strains. For example, the BALB/c parent responded to a 118-kDa component, but the SJL parent and the F1 progeny did not. Moreover, the response to a 41-kDa Ag was substantially down-regulated in the F1, whereas both parental strains responded vigorously. This new model system, therefore, has implications for MHC control of responses to the allergens of pathogens, and for the complex immunoregulation in heterozygotes in the context of infection.
人类对寄生线虫的免疫反应在抗原特异性以及生活在相同环境中个体的感染负荷方面存在很大差异。利用线虫蛔虫感染小鼠，研究了前者通过免疫系统库控制具有遗传基础的可能性。使用寄生虫的排泄/分泌（ES）物质作为靶抗原，检测抗体反应的特异性。未发现有小鼠品系能识别ES的所有潜在抗原成分，且抗原识别模式因品系而异。利用BALB和B10背景的H-2同源小鼠，确定抗原识别模式由MHC决定。聚焦于Mr 14,000的ES的一个特定成分，只有H-2s品系产生IgG反应。这种库的MHC限制仅限于感染，在用纯化蛋白进行佐剂辅助免疫时会被打破。在被动皮肤过敏试验中，Mr 14,000分子也被发现是一种强效过敏原，对其的IgE反应也仅限于H-2s。然而，在SJL背景下，这种单倍型是低IgE反应者。因此，对该分子的免疫反应特异性存在MHC控制，但对其IgE抗体反应幅度存在非MHC控制。反应品系和无反应品系（BALB/c×SJL）F1之间的杂交种对Mr 14,000有反应，但它们对其他ES成分的反应无法根据亲本品系的反应模式预测。例如，BALB/c亲本对118-kDa成分有反应，但SJL亲本和F1后代没有。此外，F1中对41-kDa抗原的反应大幅下调，而两个亲本品系反应强烈。因此，这个新的模型系统对于MHC对病原体过敏原反应的控制以及感染情况下杂合子中的复杂免疫调节具有重要意义。
