Achenbach Peter, Kelemen Katalin, Wegmann Dale R, Hutton John C
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262, USA.
J Autoimmun. 2002 Nov;19(3):111-6. doi: 10.1006/jaut.2002.0611.
Phogrin (IA-2beta), a major autoantigen in type 1 diabetes in man is recognized by peripheral T cells in the nonobese diabetic (NOD) mouse. CD4(+) T-cell clones derived from immunized NOD animals elicit islet destruction in a disease transfer model. Spontaneous proliferative responses to the protein and derived peptide epitopes were detected in peripheral lymph node cells (LNC) of unprimed NOD mice but not BALB/c controls as early as 4 weeks of age at a time point when insulitis in NOD animals is minimal. Responses to irradiated NOD islet cells but not irradiated NOD spleen cells were observed for both male and female NOD animals. Insulin, phogrin and phogrin-peptide 7 (aa 755-777) but not phogrin-peptide 2 (aa 640-659) or tetanus toxin peptide were recognized as antigens. Islet cell-reactive and phogrin peptide 7-specific CD4(+) T-cell lines were generated from splenocytes of unprimed 4-week-old NOD females and shown to secrete Th1-type cytokines. The results show that the phogrin molecule is targeted early in the course of disease in NOD animals at a time when circulating autoantibodies are absent and insulitis is minimal.
Phogrin（IA-2β）是人类1型糖尿病中的一种主要自身抗原，在非肥胖糖尿病（NOD）小鼠中可被外周T细胞识别。从免疫的NOD动物中获得的CD4(+) T细胞克隆在疾病转移模型中引发胰岛破坏。早在4周龄时，即在NOD动物胰岛炎最轻微的时间点，未致敏的NOD小鼠的外周淋巴结细胞（LNC）中就检测到了对该蛋白及其衍生肽表位的自发增殖反应，而BALB/c对照小鼠则未检测到。雄性和雌性NOD动物对经辐照的NOD胰岛细胞有反应，但对经辐照的NOD脾细胞无反应。胰岛素、Phogrin和Phogrin肽7（氨基酸755 - 777）被识别为抗原，而Phogrin肽2（氨基酸640 - 659）或破伤风毒素肽则未被识别。从未致敏的4周龄NOD雌性小鼠的脾细胞中产生了胰岛细胞反应性和Phogrin肽7特异性的CD4(+) T细胞系，并显示它们分泌Th1型细胞因子。结果表明，在NOD动物疾病进程的早期，当循环自身抗体不存在且胰岛炎最轻微时，Phogrin分子就成为了攻击目标。
