Regulation of SIV antigen-specific CD4+ T cellular immunity via autophagosome-mediated MHC II molecule-targeting antigen presentation in mice.
Regulation of SIV antigen-specific CD4+ T cellular immunity via autophagosome-mediated MHC II molecule-targeting antigen presentation in mice.
复制标题
通过小鼠自噬体介导的 MHC II 分子靶向抗原呈递调节 SIV 抗原特异性 CD4 T 细胞免疫
DOI：
10.1371/journal.pone.0093143
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Jin Y;Sun C;Feng L;Li P;Xiao L;Ren Y;Wang D;Li C;Chen L
CD 4 + T细胞介导的免疫因其在控制HIV病毒复制方面的贡献而日益受到关注，因此，提高CD 4 + T细胞应答对增强HIV疫苗的疗效具有重要意义。最近的研究表明，巨自噬在调节针对CD 4 + T细胞或CD 8 + T细胞的适应性免疫应答中起着至关重要的作用。在本研究中，一种新的策略的基础上的macroautophagy降解机制进行了调查，以提高CD 4 + T细胞对HIV/SIV gag抗原的反应。我们的研究结果表明，当融合到自噬体相关的LC 3b蛋白，SIVgag蛋白可以在功能上靶向自噬体，处理自噬介导的降解在自体溶酶体/溶酶体，提出的MHC II区室，并引发有效的潜在的CD 4 T细胞在体外的反应。重要的是，与单独的SIVgag蛋白相比，SIVgag-LC 3b融合抗原可以在小鼠中诱导更强的抗原特异性CD 4 + T细胞应答，其特征在于增强的幅度和多功能性。这项研究为病毒和哺乳动物细胞之间通过自噬进行免疫调节提供了见解，也为开发有效的HIV疫苗中新抗原的设计提供了一种替代策略。
CD4+ T cell-mediated immunity has increasingly received attention due to its contribution in the control of HIV viral replication; therefore, it is of great significance to improve CD4+ T cell responses to enhance the efficacy of HIV vaccines. Recent studies have suggested that macroautophagy plays a crucial role in modulating adaptive immune responses toward CD4+ T cells or CD8+ T cells. In the present study, a new strategy based on a macroautophagy degradation mechanism is investigated to enhance CD4+ T cell responses against the HIV/SIV gag antigen. Our results showed that when fused to the autophagosome-associated LC3b protein, SIVgag protein can be functionally targeted to autophagosomes, processed by autophagy-mediated degradation in autolysosomes/lysosomes, presented to MHC II compartments and elicit effective potential CD4 T cell responses in vitro. Importantly, compared with the SIVgag protein alone, SIVgag-LC3b fusion antigen can induce a stronger antigen-specific CD4+ T cell response in mice, which is characterized by an enhanced magnitude and polyfunctionality. This study provides insight for the immunological modulation between viral and mammalian cells via autophagy, and it also presents an alternative strategy for the design of new antigens in the development of effective HIV vaccines.
登录
查看更多内容
影响因子：
56.3
作者：
Gray, Glenda E.;Allen, Mai;Moodie, Zoe;Churchyard, Gavin;Bekker, Linda-Gail;Nchabeleng, Maphoshane;Mlisana, Koleka;Metch, Barbara;de Bruyn, Guy;Latka, Mary H.;Roux, Surita;Mathebula, Matsontso;Naicker, Nivashnee;Ducar, Constance;Carter, Donald K.;Puren, Adrien;Eaton, Niles;McElrath, M. Julie;Robertson, Michael;Corey, Lawrence;Kublin, James G.
通讯作者：
Kublin, James G.
DOI：
10.1084/jem.20110640
发表时间：
2011-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ireland JM;Unanue ER
通讯作者：
Unanue ER
影响因子：
5.4
作者：
Casimiro, DR;Tang, AM;Shiver, JW
通讯作者：
Shiver, JW
DOI：
10.1084/jem.20060134
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gauduin MC;Yu Y;Barabasz A;Carville A;Piatak M;Lifson JD;Desrosiers RC;Johnson RP
通讯作者：
Johnson RP
HIV-1 疫苗功效试验的免疫相关分析。
DOI：
10.1056/nejmoa1113425
发表时间：
2012-04-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Haynes BF;Gilbert PB;McElrath MJ;Zolla-Pazner S;Tomaras GD;Alam SM;Evans DT;Montefiori DC;Karnasuta C;Sutthent R;Liao HX;DeVico AL;Lewis GK;Williams C;Pinter A;Fong Y;Janes H;DeCamp A;Huang Y;Rao M;Billings E;Karasavvas N;Robb ML;Ngauy V;de Souza MS;Paris R;Ferrari G;Bailer RT;Soderberg KA;Andrews C;Berman PW;Frahm N;De Rosa SC;Alpert MD;Yates NL;Shen X;Koup RA;Pitisuttithum P;Kaewkungwal J;Nitayaphan S;Rerks-Ngarm S;Michael NL;Kim JH
通讯作者：
Kim JH