Different antigen-processing activities in dendritic cells, macrophages, and monocytes lead to uneven production of HIV epitopes and affect CTL recognition.
Different antigen-processing activities in dendritic cells, macrophages, and monocytes lead to uneven production of HIV epitopes and affect CTL recognition.
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DOI：
10.4049/jimmunol.1400491
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发表时间：
2014-11-01
期刊：
影响因子：
--
通讯作者：
Le Gall S
中科院分区：
文献类型：
--
作者：
Dinter J;Gourdain P;Lai NY;Duong E;Bracho-Sanchez E;Rucevic M;Liebesny PH;Xu Y;Shimada M;Ghebremichael M;Kavanagh DG;Le Gall S
树突状细胞（dc）、巨噬细胞（MPs）和单核细胞是允许HIV的。尽管肽加工和提呈对于识别和清除感染细胞至关重要，但它们是否类似地加工和呈递HIV表位给HIV特异性CD8 T细胞尚不清楚。胞质肽酶降解来自自身或病原体的内源性蛋白质，内溶酶体预处理的外源性抗原，从而形成可用于内质网（ER）易位、修剪和MHC-I呈递的肽穹。在这里，我们比较了树突状细胞、MPs和单核细胞胞浆提取物产生表位前体和表位的能力。我们发现单核细胞来源的dc和MPs之间的蛋白水解活性和胞质蛋白酶表达水平存在差异，并且在LPS， R848和CL097成熟后，成熟的MPs具有最高的活性。使用细胞质溶胶作为蛋白酶的来源来降解含有表位的HIV肽，我们通过质谱分析发现，长肽的降解模式、产生的抗原肽的动力学和数量在dc、MPs和单核细胞中是不同的。此外，HIV肽在装载到MHC之前的细胞内稳定性的变化可能会强调这些亚群之间MHC- i呈递表位可用性的差异。肽降解的差异导致dc、MPs和单核细胞中产生的降解肽引起的CTL反应差异2至25倍。这些亚群之间抗原加工活性的差异可能导致ctl识别hiv感染细胞的时间和效率的变化，并导致hiv特异性ctl控制病毒载量的能力不平等。
Dendritic cells (DCs), macrophages (MPs) and monocytes are permissive to HIV. Whether they similarly process and present HIV epitopes to HIV-specific CD8 T cells is unknown despite the critical role of peptide processing and presentation for recognition and clearance of infected cells. Cytosolic peptidases degrade endogenous proteins originating from self or pathogens, exogenous antigens preprocessed in endolysosomes, thus shaping the peptidome available for endoplasmic reticulum (ER) translocation, trimming and MHC-I presentation. Here we compared the capacity of DCs, MPs and monocyte cytosolic extracts to produce epitope precursors and epitopes. We showed differences in the proteolytic activities and expression levels of cytosolic proteases between monocyte-derived DCs and MPs and upon maturation with LPS, R848 and CL097, with mature MPs having the highest activities. Using cytosol as a source of proteases to degrade epitope-containing HIV peptides, we showed by mass spectrometry that the degradation patterns of long peptides and the kinetics and amount of antigenic peptides produced differed among DCs, MPs and monocytes. Additionally, variable intracellular stability of HIV peptides prior to loading onto MHC may accentuate the differences in epitope availability for presentation by MHC-I between these subsets. Differences in peptide degradation led to 2- to 25-fold differences in the CTL responses elicited by the degradation peptides generated in DCs, MPs and monocytes. Differences in antigen processing activities between these subsets might lead to variations in the timing and efficiency of recognition of HIV-infected cells by CTLs and contribute to the unequal capacity of HIV-specific CTLs to control viral load.
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影响因子：
32.4
作者：
Ferguson AL;Mann JK;Omarjee S;Ndung'u T;Walker BD;Chakraborty AK
通讯作者：
Chakraborty AK
DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
20.3
作者：
Fujiwara, Mamoru;Takiguchi, Masafumi
通讯作者：
Takiguchi, Masafumi
影响因子：
30.3
作者：
Jouve, Mabel;Sol-Foulon, Nathalie;Benaroch, Philippe
通讯作者：
Benaroch, Philippe
影响因子：
15.9
作者：
Beignon, AS;McKenna, K;Bhardwaj, N
通讯作者：
Bhardwaj, N