Shi Y P, Sayed U, Qari S H, Roberts J M, Udhayakumar V, Oloo A J, Hawley W A, Kaslow D C, Nahlen B L, Lal A A
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
Infect Immun. 1996 Jul;64(7):2716-23. doi: 10.1128/iai.64.7.2716-2723.1996.
We have characterized the natural immune responses to the 19-kDa domain of merozoite surface protein 1 in individuals from an area of western Kenya in which malaria is holoendemic. We used the three known natural variant forms of the yeast-expressed recombinant 19-kDa fragment that are referred to as the E-KNG, Q-KNG, and E-TSR antigens. T-cell proliferative responses in individuals older than 15 years and the profile of immunoglobulin G (IgG) antibody isotypes in individuals from 2 to 74 years old were determined. Positive proliferative responses to the Q-KNG antigen were observed for 54% of the individuals, and 37 and 35% of the individuals responded to the E-KNG and E-TSR constructs, respectively. Considerable heterogeneity in the T-cell proliferative responses to these three variant antigens was observed in different individuals, suggesting that the 19-kDa antigen may contain variant-specific T epitopes. Among responses of the different isotypes of the IgG antibody, IgG1 and IgG3 isotype responses were predominant, and the prevalence and levels of the responses increased with age. We also found that a higher level of IgG1 antibody response correlated with lower parasite density among young age groups, suggesting that IgG1 antibody response may play a role in protection against malaria. However, there was no correlation between the IgG3 antibody level and protection. Furthermore, we observed that although the natural antibodies cross-reacted with all three variant 19-kDa antigens, IgG3 antibodies in 12 plasma samples recognized only the E-KNG and Q-KNG constructs and not the E-TSR antigen. This result suggests that the fine specificity of IgG3 antibodies differentiates among variant-specific natural B-cell determinants in the second epidermal growth factor domain (KNG and TSR) of the antigen.
我们已对肯尼亚西部疟疾高度流行地区个体针对裂殖子表面蛋白1的19 kDa结构域的天然免疫反应进行了表征。我们使用了酵母表达的重组19 kDa片段的三种已知天然变体形式，分别称为E-KNG、Q-KNG和E-TSR抗原。测定了15岁以上个体的T细胞增殖反应以及2至74岁个体的免疫球蛋白G（IgG）抗体亚型谱。54%的个体对Q-KNG抗原呈现阳性增殖反应，分别有37%和35%的个体对E-KNG和E-TSR构建体有反应。在不同个体中观察到对这三种变体抗原的T细胞增殖反应存在相当大的异质性，这表明19 kDa抗原可能含有变体特异性T表位。在IgG抗体不同亚型的反应中，IgG1和IgG3亚型反应占主导，且反应的流行率和水平随年龄增加。我们还发现，在年轻年龄组中，较高水平的IgG1抗体反应与较低的寄生虫密度相关，这表明IgG1抗体反应可能在预防疟疾中发挥作用。然而，IgG3抗体水平与保护作用之间没有相关性。此外，我们观察到，尽管天然抗体与所有三种19 kDa变体抗原发生交叉反应，但12份血浆样本中的IgG3抗体仅识别E-KNG和Q-KNG构建体，而不识别E-TSR抗原。这一结果表明，IgG3抗体的精细特异性在抗原的第二个表皮生长因子结构域（KNG和TSR）中的变体特异性天然B细胞决定簇之间存在差异。
