Enhanced antigen processing of flagellin fusion proteins promotes the antigen-specific CD8+ T cell response independently of TLR5 and MyD88.
Enhanced antigen processing of flagellin fusion proteins promotes the antigen-specific CD8+ T cell response independently of TLR5 and MyD88.
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鞭毛蛋白融合蛋白的增强抗原加工可促进抗原特异性CD8+ T细胞反应，独立于TLR5和MYD88。
DOI：
10.4049/jimmunol.1001855
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Mizel SB
中科院分区：
文献类型：
--
作者：
Bates JT;Graff AH;Phipps JP;Grayson JM;Mizel SB
鞭毛蛋白是一种高效的CD 4 + T细胞和体液免疫应答的佐剂。然而，在关于鞭毛蛋白促进CD 8 + T细胞应答的能力的文献中存在矛盾的数据。在这篇文章中，我们报告了野生型、TLR 5 −/−和MyD 88 −/−过继转移受体小鼠的免疫接种，揭示了鞭毛蛋白融合蛋白促进OVA特异性CD 8 + T细胞增殖的能力，而不依赖于受体动物的TLR 5或MyD 88表达。野生型和TLR 5 −/− APC能够在体外刺激高水平的OVA特异性CD 8 + T细胞增殖，以响应含有全长OVA或SIINFEKL表位和10个侧翼氨基酸（OVAe）的鞭毛蛋白融合蛋白，但不能响应作为单独蛋白添加的OVA和鞭毛蛋白。这种效应是独立的保守区的鞭毛蛋白和单独发生在响应OVAe。比较CD 8+效应细胞的IFN-g产生，发现在用OVAe-鞭毛蛋白融合蛋白脉冲的APC表面上SIINFEKL肽-MHC I复合物的水平高于用OVA脉冲的细胞。蛋白酶体的抑制显着降低银特异性增殖响应于OVAe融合蛋白。总之，我们的数据与以下结论一致：鞭毛蛋白-OVA融合蛋白通过促进Ag加工而不是通过TLR 5和MyD 88的刺激性信号传导诱导表位特异性CD 8 + T细胞应答。我们的研究结果提出了一种可能性，即鞭毛蛋白可能是一种有效的Ag载体，在其天然状态下加工不良。
Flagellin is a highly effective adjuvant for CD4+ T cell and humoral immune responses. However, there is conflicting data in the literature regarding the ability of flagellin to promote a CD8+ T cell response. In this article, we report that immunization of wild-type, TLR5−/−, and MyD88−/− adoptive transfer recipient mice revealed the ability of flagellin fusion proteins to promote OVA-specific CD8+ T cell proliferation independent of TLR5 or MyD88 expression by the recipient animal. Wild-type and TLR5−/− APCs were able to stimulate high levels of OVA-specific CD8+ T cell proliferation in vitro in response to a flagellin fusion protein containing full-length OVA or the SIINFEKL epitope and 10 flanking amino acids (OVAe), but not to OVA and flagellin added as separate proteins. This effect was independent of the conserved regions of flagellin and occurred in response to OVAe alone. Comparison of IFN-g production by CD8+ effector cells revealed higher levels of SIINFEKL peptide–MHC I complexes on the surface of APCs that had been pulsed with OVAe–flagellin fusion proteins than on cells pulsed with OVA. Inhibition of the proteasome significantly reduced Ag-specific proliferation in response to OVAe fusion proteins. In summary, our data are consistent with the conclusion that flagellin–OVA fusion proteins induce an epitope-specific CD8+ T cell response by facilitating Ag processing and not through stimulatory signaling via TLR5 and MyD88. Our findings raise the possibility that flagellin might be an efficient Ag carrier for Ags that are poorly processed in their native state.
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DOI：
10.4049/jimmunol.0804225
发表时间：
2009-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bates JT;Uematsu S;Akira S;Mizel SB
通讯作者：
Mizel SB
影响因子：
32.4
作者：
Hou, Baidong;Reizis, Boris;DeFranco, Anthony L.
通讯作者：
DeFranco, Anthony L.
影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
影响因子：
5.5
作者：
Huleatt, James W.;Jacobs, Andrea R.;Powell, T. J.
通讯作者：
Powell, T. J.
影响因子：
3.1
作者：
Ben-Yedidia, T;Tarrab-Hazdai, R;Arnon, R
通讯作者：
Arnon, R