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在缺乏威斯科特-奥尔德里奇综合征蛋白的情况下,可溶性而非颗粒性抗原的高效抗原呈递

Efficient antigen presentation of soluble, but not particulate, antigen in the absence of Wiskott-Aldrich syndrome protein.

作者信息

Westerberg Lisa, Wallin Robert P A, Greicius Gediminas, Ljunggren Hans-Gustaf, Severinson Eva

机构信息

Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.

出版信息

Immunology. 2003 Jul;109(3):384-91. doi: 10.1046/j.1365-2567.2003.01668.x.

Abstract

B cells and dendritic cells, lacking functional Wiskott-Aldrich syndrome protein (WASP), have aberrant formation of membrane protrusions. We hypothesized that protrusions may play a role in antigen presentation, and consequently, that impaired antigen presentation may be an underlying factor of the immune deficiency in patients with Wiskott-Aldrich syndrome. In this paper, we investigated the antigen presentation capacity of B cells and dendritic cells from WASP knockout mice, using soluble and particulate antigen, to CD4+ T cells from T-cell receptor transgenic DO11.10 mice. As antigen we used soluble ovalbumin (OVA), a peptide thereof (amino acids 323-339) or bacteria expressing OVA. We found that WASP-deficient B cells and dendritic cells efficiently processed and presented soluble OVA protein as well as its peptide in vitro, inducing proliferation and cytokine production from CD4+ T cells. Antigen presentation of soluble protein was efficient also in vivo, because immunization of WASP-deficient mice with OVA elicited proliferation of transferred, fluorescent-labelled, CD4+ T cells. Although we could detect uptake of bacteria in dendritic cells, processing and presentation of bacterial-expressed OVA was impaired in WASP-deficient dendritic cells. In conclusion, our data suggest that WASP is not needed for processing and presentation of soluble antigen, but that efficient presentation of particulate antigen require WASP.

摘要

缺乏功能性威斯科特-奥尔德里奇综合征蛋白(WASP)的B细胞和树突状细胞存在膜突出物形成异常的情况。我们推测突出物可能在抗原呈递中发挥作用,因此,抗原呈递受损可能是威斯科特-奥尔德里奇综合征患者免疫缺陷的潜在因素。在本文中,我们使用可溶性和颗粒性抗原,研究了来自WASP基因敲除小鼠的B细胞和树突状细胞向T细胞受体转基因DO11.10小鼠的CD4+T细胞呈递抗原的能力。作为抗原,我们使用了可溶性卵清蛋白(OVA)、其一种肽(氨基酸323 - 339)或表达OVA的细菌。我们发现,缺乏WASP的B细胞和树突状细胞在体外能够有效地加工和呈递可溶性OVA蛋白及其肽,诱导CD4+T细胞增殖并产生细胞因子。可溶性蛋白的抗原呈递在体内也很有效,因为用OVA免疫缺乏WASP的小鼠会引发转移的、荧光标记的CD4+T细胞增殖。虽然我们能在树突状细胞中检测到细菌的摄取,但缺乏WASP的树突状细胞对细菌表达的OVA的加工和呈递受损。总之,我们的数据表明,加工和呈递可溶性抗原不需要WASP,但高效呈递颗粒性抗原需要WASP。

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