IMMUNOCHEMICAL CHARACTERIZATION OF RETINAL S-ANTIGEN

本续期申请中所述的项目一般属于 在很大程度上基于有关 视网膜S抗原的免疫化学特性及 制备的S抗原特异性T细胞系的特征和 在项目的前两年进行了分析。 I. S抗原的免疫化学 a. 进一步确定肽中的致葡萄膜表位 CB123并继续寻找其他表位 被T细胞和抗体识别，集中在T 细胞 B. 继续定位剩余的肽 在整个结构中没有被分配， 确定它们的N-末端序列用于比对， DNA预测序列。 C. 检查其他肽，因为研究的证据 人S-抗原和人S-抗原特异性T细胞系 表明另一种葡萄膜炎决定因子可能是 存在于S抗原的其他地方。 二. 免疫的抗原特异性调节 实验性自身免疫性葡萄膜视网膜炎的反应 （EAU）。 a. 我们有证据表明在同基因的 大鼠辐射S-抗原特异性细胞系诱导 在体外这些细胞系中的增殖反应，但在 PPD特异性线表明存在抗体 识别T细胞受体独特型。 这种试剂可以 在体内是非常有用的， 细胞 这种结合可以改变行为，生存能力， 这些细胞的迁移模式或能力， 免疫系统的其他元素，并可以提供一个 用于控制自身免疫的治疗有用的系统。 辅助性T细胞标志物的抗体已被证明是非免疫性的。 特异性抑制其他系统中的自身免疫; 据推测，使用更特异的抗体将 仅抑制所需的响应。 B. 由于抗独特型抗体提高到抗原特异性 已经证明抗体也结合T细胞受体 对于这种抗原，我们将测试一组抗独特型抗体 提出了抗S抗原单克隆抗体， 活动 C. 肽和肽类似物。 的类似物 含有T细胞表位但不 含有该抗原表位可以抑制T细胞的抗原活化， 细胞受体。

The projects described in this renewal application fall into general areas and are based in large measure on data regarding the immunochemical properties of retinal S-antigen and the characteristics of the S-antigen-specific T cell lines prepared and analyzed during the first two years of the project. I. IMMUNOCHEMISTRY OF S-ANTIGEN. a. Further delineate the uveitogenic epitope in peptide CB123 and continue the search for other epitopes recognized by T cells and antibodies, concentrating on the T cells. b. Continue the localization of the remaining peptides which have not been assigned in the overall structure by determining their N-terminal sequence for alignment in DNA-predicted sequences. c. Examine other peptides since evidence from studies with human S-antigen and a human S-antigen-specific T cell line indicates that another uveitogenic determinant may be present elswhere in S-antigen. II. ANTIGEN-SPECIFIC MODULATION OF THE IMMUNE RESPONSES IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU). a. We have evidence that an antibody raised in syngeneic rats to irradiated S-antigen-specific cell lines induces a proliferative response in those line cells in vitro, but not in a PPD-specific line suggesting the presence of antibody recognizing T cell receptor idiotype. Such a reagent could be very useful in vivo where it would specifically bind those cells. Such binding could alter the behavior, viability, migratory patterns or ability of those cells to interact with other elements of the immune system and could provide a therapeutically usefuls system for controlling autoimmunity. Antibodies to the T helper markers have been shown to non- specifically suppress autoimmunity in other systems; presumably the use of a more specific antibody would suppress only the desired response. b. Since anti-idiotypic antibodies raised to antigen-specific antibodies have been shown to also bind the T cell receptor for that antigen, we will test a group of anti-idiotypes raised to anti-S-antigen monoclonal antibodies for such activity. c. Peptides and peptide analogues. An analogue of the peptide which contains the T cell epitope but does not contain the agretope may inhibit antigen activation of the T cell receptor.