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Presentation of Toxoplasma gondii Antigens via the Endogenous Major Histocompatibility Complex Class I Pathway in Nonprofessional and Professional Antigen-Presenting Cells▿

机译：在非专业和专业抗原呈递细胞中通过内源性主要组织相容性复合体I类途径呈递弓形虫抗原▿

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摘要

Challenge with the intracellular protozoan parasite Toxoplasma gondii induces a potent CD8+ T-cell response that is required for resistance to infection, but many questions remain about the factors that regulate the presentation of major histocompatibility complex class I (MHC-I)-restricted parasite antigens and about the role of professional and nonprofessional accessory cells. In order to address these issues, transgenic parasites expressing ovalbumin (OVA), reagents that track OVA/MHC-I presentation, and OVA-specific CD8+ T cells were exploited to compare the abilities of different infected cell types to stimulate CD8+ T cells and to define the factors that contribute to antigen processing. These studies reveal that a variety of infected cell types, including hematopoietic and nonhematopoietic cells, are capable of activating an OVA-specific CD8+ T-cell hybridoma, and that this phenomenon is dependent on the transporter associated with antigen processing and requires live T. gondii. Several experimental approaches indicate that T-cell activation is a consequence of direct presentation by infected host cells rather than cross-presentation. Surprisingly, nonprofessional antigen-presenting cells (APCs) were at least as efficient as dendritic cells at activating this MHC-I-restricted response. Studies to assess whether these cells are involved in initiation of the CD8+ T-cell response to T. gondii in vivo show that chimeric mice expressing MHC-I only in nonhematopoietic compartments are able to activate OVA-specific CD8+ T cells upon challenge. These findings associate nonprofessional APCs with the initial activation of CD8+ T cells during toxoplasmosis.
机译：用细胞内的原生动物寄生虫进行攻击弓形虫会诱导有效的CD8 + T细胞应答，这是抵抗感染所必需的，但有关调节主要组织相容性复合体I类（MHC-1）限制的寄生虫抗原呈递的因素仍存在许多疑问以及专业和非专业辅助细胞的作用。为了解决这些问题，利用表达卵清蛋白（OVA）的转基因寄生虫，跟踪OVA / MHC-1呈递的试剂以及OVA特异性CD8 + T细胞来比较不同感染细胞类型刺激CD8 + T细胞和确定有助于抗原加工的因素。这些研究表明，包括造血和非造血细胞在内的多种感染细胞能够激活OVA特异性CD8 + T细胞杂交瘤，并且这种现象取决于与抗原加工相关的转运蛋白，并且需要活弓形虫。 。几种实验方法表明，T细胞活化是被感染宿主细胞直接呈递而不是交叉呈递的结果。出人意料的是，非专业抗原呈递细胞（APC）在激活这种MHC-1限制性反应方面至少与树突状细胞一样有效。评估这些细胞是否参与体内针对弓形虫的CD8 + T细胞反应的研究表明，仅在非造血区室中表达MHC-1的嵌合小鼠能够在攻击后激活OVA特异性CD8 + T细胞。这些发现将非专业APC与弓形体病期间CD8 + T细胞的初始激活相关联。

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