Westerberg Lisa, Wallin Robert P A, Greicius Gediminas, Ljunggren Hans-Gustaf, Severinson Eva
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Immunology. 2003 Jul;109(3):384-91. doi: 10.1046/j.1365-2567.2003.01668.x.
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.
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。