Sireci G, Dieli F, Caccamo N, Barera A, Carta P, Di Sano C, Meraviglia S, Bonanno C T, Salerno A
Department of Biopathology, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
Scand J Immunol. 2003 Aug;58(2):188-94. doi: 10.1046/j.1365-3083.2003.01296.x.
Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA-restricted presentation of T-cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA-DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13-33, 87-106 and 139-154 bound by HLA-DR1. We report here that HLA-DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13-33 epitope induced a strong T helper 1 (Th1) response accompanied by high T-cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139-154) or no disease (87-106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.
现在有大量证据表明，人类白细胞抗原（HLA）I类和II类转基因（Tg）小鼠在分析与自身免疫性疾病实验模型相关的T细胞表位的HLA限制呈递方面具有价值。这一应用领域之一是在多发性硬化症实验模型（实验性变应性脑脊髓炎（EAE））中对HLA II类分子呈递的髓磷脂表位进行表征。作为在HLA Tg小鼠中建立人源化疾病模型的第一步，我们分析了用与HLA-DR1结合的人髓磷脂碱性蛋白（MBP）肽13 - 33、87 - 106和139 - 154免疫的HLA-DR1 Tg小鼠淋巴结细胞的免疫反应。我们在此报告，HLA-DR1 Tg小鼠在体内和体外对MBP表位的反应具有层级性，这取决于与DRB*0101分子的结合亲和力。事实上，13 - 33表位诱导了强烈的辅助性T细胞1（Th1）反应，伴有高T细胞前体频率，并导致轻度EAE，而另外两个表位引发的疾病较轻（139 - 154）或不引发疾病（87 - 106），这些数据与体外Th1反应相关。这些数据可能成为理解不同MBP表位在EAE中所起作用的有用工具。
