de Smet M D, Bitar G, Roberge F G, Gery I, Nussenblatt R B
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892.
J Autoimmun. 1993 Oct;6(5):587-99. doi: 10.1006/jaut.1993.1048.
To identify the immunogenic and immunopathogenic sites present in human S-Antigen (S-Ag), 40 overlapping peptides that span the whole length of the S-Ag molecule were synthesized and tested in the Lewis rat model of experimental autoimmune uveitis. The most pathogenic sequences were 180-200, 340-360 and 350-370. Ten peptide sequences were identified that induced visible inflammation in the eye. A total of 23 peptides gave an in-vitro proliferative response following immunization in animals. The ability to generate an immune response was not linked to the pathogenic capacity of the sequence. The most pathogenic sequence, 340-360, was only weakly proliferative. Peptide 180-200 and peptide 340-360 gave higher T-cell proliferative responses, but these were lower than the maximal proliferative response observed with non-pathogenic sequences. In animals immunized with whole S-Ag, the majority of the determinants did not elicit a proliferative response, indicating that in S-Ag, the majority of the immunogenic determinants are cryptic and are not presented by the APC located in the lymph nodes.
为了鉴定人S抗原(S-Ag)中存在的免疫原性和免疫致病位点,合成了覆盖S-Ag分子全长的40个重叠肽,并在实验性自身免疫性葡萄膜炎的Lewis大鼠模型中进行了测试。最具致病性的序列是180-200、340-360和350-370。鉴定出10个能在眼中诱导可见炎症的肽序列。总共23个肽在动物免疫后产生了体外增殖反应。产生免疫反应的能力与序列的致病能力无关。最具致病性的序列340-360增殖能力较弱。肽180-200和肽340-360产生了较高的T细胞增殖反应,但低于非致病序列观察到的最大增殖反应。在用完整S-Ag免疫的动物中,大多数决定簇未引发增殖反应,这表明在S-Ag中,大多数免疫原性决定簇是隐蔽的,且未被位于淋巴结中的抗原呈递细胞呈递。