Utsugi-Kobukai Saho, Fujimaki Haruka, Hotta Chie, Nakazawa Masatoshi, Minami Mutsuhiko
Department of Immunology, Yokohama City University, School of Medicine, 3-9 Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan.
Immunol Lett. 2003 Oct 31;89(2-3):125-31. doi: 10.1016/s0165-2478(03)00128-7.
Exosomes are 50-90 nm vesicles with antigen presenting ability carrying major histocompatibility complex (MHC) class I, class II, abundant co-stimulatory molecules and some tetraspan proteins. Although dendritic cells (DCs) are one of the professional antigen presenting cells capable of presenting exogenous antigens in MHC class I-mediated antigen specific manner (cross-presentation), the cross-presentation ability by exosomes from immature or mature DCs are unknown. Here we show that exosomes released from ovalbumin (OVA) protein-pulsed bone marrow derived dendritic cells (BM-DCs) weakly present the peptide determinants to OVA specific MHC class I-restricted CD8(+) T cell hybridomas. The exosomes secreted by OVA(257-264) peptide- or OVA protein-pulsed mature BM-DCs activated OVA specific MHC class I-restricted T cell hybridomas more efficiently than those from immature BM-DCs. Transporters associated with antigen processing (TAP) deficient mice-derived BM-DCs were also used to examine whether functional TAP activity was required for cross-presentation by exosomes. The exosomes obtained from OVA(257-264) peptide-pulsed BM-DCs derived from TAP(-/-) mice showed a significant antigen presenting ability to OVA specific MHC class I-restricted T cell hybridomas. Altogether, our data indicate that BM-DCs secrete exosomes with weak cross-presentation ability.
外泌体是50-90纳米的囊泡,具有抗原呈递能力,携带主要组织相容性复合体(MHC)I类、II类、丰富的共刺激分子和一些四跨膜蛋白。尽管树突状细胞(DCs)是能够以MHC I类介导的抗原特异性方式呈递外源性抗原(交叉呈递)的专职抗原呈递细胞之一,但来自未成熟或成熟DCs的外泌体的交叉呈递能力尚不清楚。在此我们表明,从卵清蛋白(OVA)蛋白脉冲的骨髓来源树突状细胞(BM-DCs)释放的外泌体将肽决定簇微弱地呈递给OVA特异性MHC I类限制性CD8(+) T细胞杂交瘤。OVA(257-264)肽或OVA蛋白脉冲的成熟BM-DCs分泌的外泌体比未成熟BM-DCs分泌的外泌体更有效地激活OVA特异性MHC I类限制性T细胞杂交瘤。与抗原加工相关的转运体(TAP)缺陷小鼠来源的BM-DCs也被用于检查外泌体交叉呈递是否需要功能性TAP活性。从TAP(-/-)小鼠来源的OVA(257-264)肽脉冲的BM-DCs获得的外泌体对OVA特异性MHC I类限制性T细胞杂交瘤显示出显著的抗原呈递能力。总之,我们的数据表明BM-DCs分泌具有弱交叉呈递能力的外泌体。