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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:通过非专业和专业抗原呈递细胞中的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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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:细胞内原生动物寄生虫<弓形虫>弓形虫的刺激诱导了有效的CD8 + T细胞反应,这是抵抗感染所必需的,但是关于调节表达的因素仍有许多疑问主要组织相容性复合物I类(MHC-I)限制的寄生虫抗原的研究,以及有关专业和非专业辅助细胞的作用。为了解决这些问题,研究人员利用表达卵清蛋白(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的能力。刺激CD8 + T细胞的类型,并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之相关的转运蛋白。抗原加工,需要活的T。刚地。几种实验方法表明,T细胞活化是受感染宿主细胞直接呈递而不是交叉呈递的结果。令人惊讶地,非专业抗原呈递细胞(APC)在激活该MHC-1限制性反应中至少与树突状细胞一样有效。评估这些细胞是否参与CD8 + T细胞对 T应答的研究。刚地体内显示,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。这些发现将非专业的APC与弓形虫病期间CD8 + T细胞的初始活化相关。

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