Immunodominant T cell determinants of aquaporin-4, the autoantigen associated with neuromyelitis optica.
Immunodominant T cell determinants of aquaporin-4, the autoantigen associated with neuromyelitis optica.
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DOI：
10.1371/journal.pone.0015050
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发表时间：
2010-11-30
期刊：
影响因子：
3.7
通讯作者：
Zamvil SS
中科院分区：
文献类型：
--
作者：
Nelson PA;Khodadoust M;Prodhomme T;Spencer C;Patarroyo JC;Varrin-Doyer M;Ho JD;Stroud RM;Zamvil SS
视神经脊髓炎(NMO)中针对水通道蛋白4(AQP4)的自身抗体是IgG1，这是一种T细胞依赖的Ig亚类。然而，AQP4特异性T细胞在这种中枢神经系统炎症性疾病中的作用尚不清楚。为了评估它们在中枢神经系统自身免疫中的潜在作用，我们在C57BL/6和SJL/J小鼠中鉴定了对AQP4有反应的T细胞，这两个品系是在中枢神经系统炎症性疾病模型中经常研究的两个菌株。用重叠的多肽或包含整个323个氨基酸序列的完整hAQP4蛋白免疫小鼠。通过对AQP4多肽(P)文库的检测，发现C57BL/6小鼠AQP4基因位于p21-40、p91-110、p101-120、p166-180、p231-250和p261-280之间，而SJL/J小鼠则位于p11-30、p21-40、p101-120、p126-140和P261-280之间。AQP4特异性T细胞为CD4+和MHC II限制性T细胞。在对完整AQP4免疫的回忆反应中，T细胞主要与p21-40反应，表明该区域包含两个毒株的免疫优势T细胞表位(S)。AQP4p21-40诱导的T细胞分泌干扰素-γ和IL-17。核心免疫优势的AQP4 21-40 T细胞决定簇在C57BL/6小鼠和SJL/J小鼠中分别定位于24-35位和23-35位。我们对AQP4 T细胞决定簇的鉴定及其免疫优势决定簇的特征将使研究人员能够评估AQP4特异性T细胞在体内的作用，并建立AQP4靶向的小鼠NMO模型。
Autoantibodies that target the water channel aquaporin-4 (AQP4) in neuromyelitis optica (NMO) are IgG1, a T cell-dependent Ig subclass. However, a role for AQP4-specific T cells in this CNS inflammatory disease is not known. To evaluate their potential role in CNS autoimmunity, we have identified and characterized T cells that respond to AQP4 in C57BL/6 and SJL/J mice, two strains that are commonly studied in models of CNS inflammatory diseases. Mice were immunized with either overlapping peptides or intact hAQP4 protein encompassing the entire 323 amino acid sequence. T cell determinants identified from examination of the AQP4 peptide (p) library were located within AQP4 p21-40, p91-110, p101-120, p166-180, p231-250 and p261-280 in C57BL/6 mice, and within p11-30, p21-40, p101-120, p126-140 and p261-280 in SJL/J mice. AQP4-specific T cells were CD4+ and MHC II-restricted. In recall responses to immunization with intact AQP4, T cells responded primarily to p21-40, indicating this region contains the immunodominant T cell epitope(s) for both strains. AQP4 p21-40-primed T cells secreted both IFN-γ and IL-17. The core immunodominant AQP4 21-40 T cell determinant was mapped to residues 24-35 in C57BL/6 mice and 23-35 in SJL/J mice. Our identification of the AQP4 T cell determinants and characterization of its immunodominant determinant should permit investigators to evaluate the role of AQP4-specific T cells in vivo and to develop AQP4-targeted murine NMO models.
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影响因子：
11.2
作者：
Bennett, Jeffrey L.;Lam, Chiwah;Kalluri, Sudhakar Reddy;Saikali, Philippe;Bautista, Katherine;Dupree, Cecily;Glogowska, Magdalena;Case, David;Antel, Jack P.;Owens, Gregory P.;Gilden, Don;Nessler, Stefan;Stadelmann, Christine;Hemmer, Bernhard
通讯作者：
Hemmer, Bernhard
DOI：
10.1084/jem.155.3.734
发表时间：
1982-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Isakson PC;Puré E;Vitetta ES;Krammer PH
通讯作者：
Krammer PH
影响因子：
14.5
作者：
Takahashi, Toshiyuki;Fujihara, Kazuo;Itoyama, Yasuto
通讯作者：
Itoyama, Yasuto
DOI：
10.1073/pnas.0902725106
发表时间：
2009-05-05
影响因子：
11.1
作者：
Ho, Joseph D.;Yeh, Ronald;Stroud, Robert M.
通讯作者：
Stroud, Robert M.
影响因子：
4.4
作者：
Stüve, O;Youssef, S;Zamvil, SS
通讯作者：
Zamvil, SS