Sanui H, Redmond T M, Hu L H, Kuwabara T, Margalit H, Cornette J L, Wiggert B, Chader G J, Gery I
Laboratory of Immunol, National Eye Institute, Bethesda, MD 20892.
Curr Eye Res. 1988 Jul;7(7):727-35. doi: 10.3109/02713688809033202.
In an earlier study we isolated three cyanogen bromide cleavage fragments of bovine IRBP that exhibited high levels of immunopathogenicity, producing inflammatory changes in the eyes (EAU) and pineal gland (EAP) of Lewis rats. These fragments have been localized within the IRBP sequence. In order to identify these putative immunopathogenic epitopes of IRBP, nine selected peptide sequences were synthesized and tested for the induction of disease in Lewis rats. Seven of the peptides were found inactive in producing disease while two closely related peptides, designated R4 (23-mer) and R9 (27-mer) were found to reproducibly induce EAU and EAP in immunized rats. No good correlation was found between the immunopathogenicity of the nine tested peptides and their amphipathicity: peptides R4 and R9 were not predicted to form strong amphipathic helices, while peptides selected for their high predicted helical amphipathicity were not immunopathogenic. EAU induced by peptides R4 and R9 was less severe and had a longer onset time than the disease induced by whole IRBP. In addition, the inflammatory changes induced by R4 and R9 in the posterior segment of the eye were less acute than those induced by whole IRBP and included granuloma formation and perivasculitis, features which are not generally seen in rats immunized with whole IRBP. Thus, the changes induced by R4 and R9 more closely resemble those which are characteristically found in human eyes affected by certain uveitic diseases than do changes produced by the intact protein.
在早期的一项研究中，我们分离出了牛视网膜间维生素A结合蛋白（IRBP）的三个溴化氰裂解片段，这些片段表现出高水平的免疫致病性，可在Lewis大鼠的眼睛（实验性自身免疫性葡萄膜炎，EAU）和松果体（实验性自身免疫性松果体炎，EAP）中引起炎症变化。这些片段已定位在IRBP序列内。为了鉴定IRBP这些假定的免疫致病表位，合成了九个选定的肽序列，并在Lewis大鼠中测试其诱发疾病的能力。发现其中七个肽在诱发疾病方面无活性，而两个密切相关的肽，命名为R4（23肽）和R9（27肽），发现在免疫大鼠中可重复性地诱发EAU和EAP。在所测试的九个肽的免疫致病性与其两亲性之间未发现良好的相关性：肽R4和R9预计不会形成强两亲性螺旋，而因其高预测螺旋两亲性而选择的肽则无免疫致病性。肽R4和R9诱发的EAU比整个IRBP诱发的疾病症状较轻且发病时间较长。此外，R4和R9在眼后段诱发的炎症变化不如整个IRBP诱发的变化剧烈，包括肉芽肿形成和血管周围炎，这些特征在用整个IRBP免疫的大鼠中一般未见。因此，与完整蛋白产生的变化相比，R4和R9诱发的变化更类似于在受某些葡萄膜疾病影响的人眼中典型发现的变化。
