A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells
A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells
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DOI：
10.1038/srep27206
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发表时间：
2016-06-02
影响因子：
4.6
通讯作者：
Ali, Nahid
中科院分区：
文献类型：
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作者：
Maji, Mithun;Mazumder, Saumyabrata;Ali, Nahid
预防利什曼原虫等细胞内感染的最有效策略是接种活寄生虫疫苗。使用重组蛋白可以避免与活疫苗相关的风险。然而，由于免疫原性低，它们不能触发T细胞反应，特别是持续免疫所需的CD8(+)细胞。在此之前，我们展示了在阳离子脂质体中包裹蛋白质的重要性，以及MPL作为佐剂在诱导CD4(+)和CD8(+)T细胞反应方面的长期保护作用。在这项研究中，我们研究了阳离子脂质体对树突状细胞(DC)成熟和抗原提呈能力的影响。我们观察到，阳离子脂质体被DC非常有效地摄取，并被转运到不同的细胞部位。脂质体rgp63激活的DC能有效地将抗原递呈给特异性的CD4(+)和CD8(+)T细胞。此外，脂质体rgp63免疫小鼠的CD8(+)T细胞在体外与刺激的DC共培养时表现出更好的增殖能力。与游离抗原和脂质体抗原相比，疫苗中加入MPL可增强DC的抗原提呈，并诱导更有效的抗原特异性CD8(+)T细胞反应。这些脂质体通过TAP依赖的MHC-I途径提供给CD8(+)T细胞，为安全的亚单位疫苗提供了新的可能性。
The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8(+) cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4(+) and CD8(+) T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4(+) and CD8(+) T cells. Furthermore, lymphoid CD8(+) T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8(+) T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8(+) T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.