Antigen/MHC class II/Ig dimers for study of uveitogenic T cells: IRBP p161-180 presented by both IA and IE molecules
Antigen/MHC class II/Ig dimers for study of uveitogenic T cells: IRBP p161-180 presented by both IA and IE molecules
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DOI：
10.1167/iovs.05-0187
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发表时间：
2005-10-01
影响因子：
4.4
通讯作者：
Caspi, RR
中科院分区：
文献类型：
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作者：
Karabekian, Z;Lytton, SD;Caspi, RR
目的.免疫显性表位特异性效应T细胞的检测和调节是自身免疫性疾病的中心问题。实验性自身免疫性葡萄膜炎是在B10中诱导的人类自身免疫性葡萄膜炎的模型。RIII小鼠与感光细胞间类维生素A结合蛋白或其免疫显性表位编码的残基161- 180。作者产生了由p161-180与IA（r）和小鼠IgG 1框内融合组成的二聚体，并研究了其对p161-180特异性的CD 4（+）葡萄膜致炎T细胞系和该细胞系衍生的T细胞克隆的影响。用肽/IA（r）/IG二聚体对T细胞系进行免疫荧光染色，结果显示约90%的细胞与试剂结合，10%的细胞没有结合。T细胞克隆未能结合试剂。与此一致，当用试剂加抗CD 28刺激时，细胞系增殖，而克隆则没有。相反，在与没有CD 28交联的试剂一起孵育后，该细胞系在随后的刺激暴露于p161-180时显示出增殖降低，而克隆不受影响。B10脾细胞的抗原特异性增殖。用p161-180引发的RIII小鼠被抗IA和抗IE抗体抑制; T细胞系的增殖被抗IA强烈抑制，而被抗IE抑制得很差，克隆显示出相反的模式。最后，该细胞系（而非克隆）增殖至p161-180，呈现在表达IA（r）作为其唯一限制性元件的B细胞淋巴瘤上。葡萄膜原性T细胞可以被检测到，以及与其同源的肽类II试剂的功能调节，这表明这种试剂的潜力，用于诊断和治疗葡萄膜炎疾病的使用; p161-180可以由IA（r）以及IEr主要组织相容性复合体（MHC）II类分子。当考虑肽-MHC试剂的诊断或临床用途时，应考虑到同一免疫显性片段可能由一种以上的II类分子呈递的可能性。
PURPOSE. Detection and modulation of effector T cells specific to immunodominant epitopes is a central issue in autoimmune diseases. Experimental autoimmune uveitis is a model for human autoimmune uveitis, induced in B10. RIII mice with interphotoreceptor retinoid binding protein or with its immunodominant epitope encoded by residues 161-180.METHODS. The authors generated a dimer composed of p161-180 fused in frame to IA(r) and mouse IgG1, and studied its effects on a CD4(+) uveitogenic T-cell line specific to p161-180 and on a T-cell clone derived from that line.RESULTS. Immunofluorescent staining of the T-cell line with the peptide/IA(r)/Ig dimer revealed that about 90% of the cells bound the reagent, and 10% did not. The T-cell clone failed to bind the reagent. Consistent with this, the line proliferated when stimulated with the reagent plus anti-CD28, and the clone did not. Conversely, after being incubated with the reagent without CD28 cross-linking, the line showed decreased proliferation on subsequent stimulatory exposure to p161-180, whereas the clone was unaffected. Antigen-specific proliferation of splenocytes from B10. RIII mice primed with p161-180 was inhibited by anti-IA as well as anti-IE antibodies; proliferation of the T-cell line was inhibited strongly by anti-IA and poorly by anti-IE, and the clone showed the opposite pattern. Finally, the line, but not the clone, proliferated to p161-180 presented on a B-cell lymphoma expressing IA(r) as its only restriction element.CONCLUSIONS. Uveitogenic T cells can be detected as well as functionally modulated with their cognate peptide-class II reagent, suggesting the potential of such reagents for diagnostic and therapeutic use in uveitic disease; p161-180 can be presented by IA(r) as well as IEr major histocompatibility complex (MHC) class II molecules. The possibility that the same immunodominant fragment might be presented by more than one class II molecule should be taken into account when diagnostic or clinical use of peptide-MHC reagents is considered.