Brown W C, McGuire T C, Zhu D, Lewin H A, Sosnow J, Palmer G H
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.
J Immunol. 2001 Jan 15;166(2):1114-24. doi: 10.4049/jimmunol.166.2.1114.
Genogroup II ehrlichia, including the agent of human granulocytic ehrlichiosis, Ehrlichia phagocytophila, and the bovine pathogen Anaplasma marginale, express a markedly immunodominant outer membrane protein designated major surface protein 2 (MSP2). MSP2 is encoded by a multigene family, resulting in the expression of variant B cell epitopes. MSP2 variants are sequentially expressed in the repeated cycles of rickettsemia that characterize persistent A. marginale infection and control of each rickettsemic cycle is associated with development of a variant-specific IgG response. Importantly, these persistent rickettsemic cycles are controlled at levels 100-1000 times lower than those responsible for clinical disease during acute infection. Control of rickettsemia during persistence could result from an anamnestic Th lymphocyte response to conserved regions of MSP2 that enhances the primary Ab response against newly emergent variants. Comparison of MSP2 variants reveals conserved N and C termini flanking the central, surface-exposed hypervariable region that represents the variant B lymphocyte epitopes. We demonstrate MSP2-specific CD4(+) T lymphocyte recognition of epitopes common to several strains of A. marginale and the related pathogen A. ovis. Furthermore, T lymphocyte lines from three individuals identified six to nine overlapping peptides representing a minimum of four to seven dominant or subdominant epitopes in these conserved N and C termini. Immunodominant peptides induced high levels of IFN-gamma, a cytokine associated with protection against ehrlichia and needed for rapid generation of variant-specific IgG2. The presented data support the potential importance of a strong Th lymphocyte response to invariant MSP2 epitopes in controlling rickettsemia during persistent infection to subclinical levels.
基因 II 群埃立克体，包括人类粒细胞埃立克体病的病原体嗜吞噬细胞无形体，以及牛病原体边缘无浆体，表达一种明显具有免疫显性的外膜蛋白，称为主要表面蛋白 2（MSP2）。MSP2 由一个多基因家族编码，导致变体 B 细胞表位的表达。MSP2 变体在无浆体血症的重复周期中依次表达，这是持续性边缘无浆体感染的特征，并且每个无浆体血症周期的控制与变体特异性 IgG 反应的发展相关。重要的是，这些持续性无浆体血症周期的控制水平比急性感染期间导致临床疾病的水平低 100 - 1000 倍。持续性感染期间无浆体血症的控制可能源于对 MSP2 保守区域的回忆性 Th 淋巴细胞反应，该反应增强了针对新出现变体的初次抗体反应。对 MSP2 变体的比较揭示了在代表变体 B 淋巴细胞表位的中央表面暴露高变区两侧的保守 N 端和 C 端。我们证明了 MSP2 特异性 CD4(+) T 淋巴细胞对几种边缘无浆体菌株和相关病原体绵羊无浆体共有的表位的识别。此外，来自三个个体的 T 淋巴细胞系鉴定出六到九个重叠肽，这些肽在这些保守的 N 端和 C 端代表至少四到七个显性或亚显性表位。免疫显性肽诱导高水平的 IFN -γ，IFN -γ 是一种与抵抗埃立克体有关的细胞因子，是快速产生变体特异性 IgG2 所必需的。所呈现的数据支持了在持续性感染期间将无浆体血症控制在亚临床水平时，强烈的 Th 淋巴细胞对不变的 MSP2 表位的反应具有潜在重要性。
