T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein I
T cells from induced and spontaneous models of SLE recognize a common T cell epitope on β2-glycoprotein I
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DOI：
10.1038/s41423-018-0013-3
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发表时间：
2019-08-01
影响因子：
24.1
通讯作者：
Rauch, Joyce
中科院分区：
文献类型：
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作者：
Salem, David;Subang, Rebecca;Rauch, Joyce
系统性红斑狼疮是自身免疫中 B 细胞表位扩散的原型模型。针对许多分子上不同的自身抗原的自身抗体在几年内以连续的方式出现，导致疾病表现。最早出现的自身抗体是针对磷脂结合蛋白，特别是 β2-糖蛋白 I 的抗体。值得注意的是，用 β2-糖蛋白 I 和脂多糖免疫的小鼠会对 β2-糖蛋白 I 产生强烈的 T 细胞反应，这与自身抗体的产生和肾脏疾病有关，类似于人类 SLE 中的情况。在此，我们假设患有小鼠系统性红斑狼疮的小鼠，无论是诱导性还是自发性，都应该具有识别 β2-糖蛋白 I 的 T 细胞。我们评估了诱导性（C57BL/6 和 C3H/HeN）和自发性（MRL/lpr）系统性红斑狼疮小鼠的脾 T 细胞对跨越人类 β2GPI 整个序列的肽的反应。我们发现诱导性和自发性系统性红斑狼疮小鼠识别 β2-糖蛋白 I 结构域 III 中的共同 T 细胞表位（肽 31；LYRDTAVFECLPQHAMFG）。来自两种模型的 β2GPI 反应性 CD4(+) T 细胞主要在细胞因子产生方面存在差异：诱导性 SLE 小鼠的 T 细胞表达 IFN-γ，而来自 MRL/lpr 小鼠的 T 细胞表达 IL-17 和 IL-17。 IFN-gamma，表明表达 IL-17 的 T 细胞对于产生 β2GPI 反应性 T 细胞反应不是必需的。这些数据表明，系统性红斑狼疮的诱导模型和自发模型都产生β2-糖蛋白I反应性T细胞反应，并且这种T细胞反应可能介导两种模型中表位扩散至自身抗体。
Systemic lupus erythematosus is a prototypic model for B-cell epitope spread in autoimmunity. Autoantibodies to numerous molecularly distinct self-antigens emerge in a sequential manner over several years, leading to disease manifestations. Among the earliest autoantibodies to appear are those targeting phospholipid-binding proteins, particularly beta 2-glycoprotein I. Notably, mice immunized with beta 2-glycoprotein I and lipopolysaccharide develop a strong T cell response to beta 2-glycoprotein I that is associated with autoantibody production and renal disease, similar to that seen in human SLE. Here we hypothesized that mice with murine systemic lupus erythematosus, whether induced or spontaneous, should have T cells that recognize beta 2-glycoprotein I. We evaluated the response of splenic T cells from mice with induced (C57BL/6 and C3H/HeN) and spontaneous (MRL/lpr) systemic lupus erythematosus to peptides spanning the entire sequence of human beta 2GPI. We found that mice with induced and spontaneous systemic lupus erythematosus recognize a common T cell epitope (peptide 31; LYRDTAVFECLPQHAMFG) in domain III of beta 2-glycoprotein I. beta 2GPI-reactive CD4(+) T cells from the two models differed primarily in cytokine production: T cells from mice with induced SLE expressed IFN-gamma, while T cells from MRL/lpr mice expressed both IL-17 and IFN-gamma, indicating that IL-17-expressing T cells are not necessary for generating a beta 2GPI-reactive T cell response. These data suggest that the generation of a beta 2-glycoprotein I-reactive T cell response is shared by both induced and spontaneous models of systemic lupus erythematosus and that this T cell response may mediate epitope spread to autoantibodies in both models.