S-ANTIGEN--STRUCTURE/FUNCTION RELATIONSHIPS IN UVEITIS

S-抗原——葡萄膜炎中的结构/功能关系

• 批准号: 3259881
• 负责人: LARRY A DONOSO
• 金额: $ 14.84万
• 依托单位: WILLS EYE HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-09-30 至 1992-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3259881
• 关键词: ADP ribosylation; DNA; antigens; autoimmune disorder; biological polymorphism; chemical binding; chemical structure function; conformation; disease /disorder model; enzyme linked immunosorbent assay; genetic library; genome; high performance liquid chromatography; histochemistry /cytochemistry; hybridomas; immunochemistry; immunofluorescence technique; laboratory mouse; laboratory rat; monoclonal antibody; oligonucleotides; pathologic process; peptide chemical synthesis; peptides; protein sequence; spectrometry; tissue /cell culture; uveitis

S-antigen is a well-characterized retinal protein, intimately involved in the visual process, and highly pathogenic for the induction of experimental autoimmune uveitis (EAU), and intimately involved in the phototransduction of vision. In order to more fully understand structure/function relationships of S- antigen in the pathogenesis of EAU and in the phototransduction of vision we have (1) produced monoclonal antibodies (MAbs) which define different epitopes of S-antigen, (2) determined the amino acid sequence of bovine S-antigen, (3) localized one MAb binding site and (4) localized two uveitopathogenic sites in bovine S-antigen. In our laboratory, we have generated two MAbs, MAbA9-C6 and MAbA1-G5, which define different epitopes of S-antigens. These MAbs have been useful in our studies concerning S-antigen in the developing retina, pineal gland and in tumors arising from these tissues. The amino acid sequence of bovine S-antigen has now been determined. Analysis of our sequence data has revealed that; S-antigen exists primarily in a beta sheet conformation; contains two potential phorphorylation sites; three potential carbohydrate attachments sites; an ADP-ribosylation site; and sequence homologies to tranducin, another protein in the visual pathway. Such information is essential in order to understand the role of S-antigen in the phototransduction of vision. A knowledge of the amino acid sequence has also led to the identification of the MAbA9-C6 binding site and two uveitopathogenic sites. Peptides, corresponding to the amino acid sequence of S-antigen, have been synthesized chemically and two peptides designated peptide K and peptide M have been found to be highly uveitopathogenic. Immunization of Lewis rats with microgram amounts of either peptides induced an EAU which was clinically and histopathologically indistinguishable from the EAU induced by native S-antigen. In this continuation proposal we plan to refine and expand our initial observations regarding the uveitopathogenic sites in bovine, human and rat S-antigen. In addition, we propose to produce MAbs against the uveitopathogenic determinants and to refine the MAbA9-C6 binding site to the resolution of a single amino acid. These studies and the reagents we are developing will not only aid in understanding the role of S-antigen in the pathogenesis of EAU, but in the phototransduction of vision as well.

s抗原是一种特性良好的视网膜蛋白

项目成果

Identification of an S-antigen-like molecule in human choroid plexus and cerebrospinal fluid.

人脉络丛和脑脊液中 S 抗原样分子的鉴定。

• DOI: 10.1038/eye.1992.128
• 发表时间: 1992
• 期刊: Eye (London, England)
• 作者: Dua,HS;Reyes,PF;Barrett,JA;Abrams,MS;Schwarting,R;Craft,CM;Donoso,LA
• 通讯作者: Donoso,LA

Immunohistochemistry of retinoblastoma. A review.

视网膜母细胞瘤的免疫组织化学。

• DOI: 10.3109/13816818909083770
• 发表时间: 1989
• 期刊: Ophthalmic paediatrics and genetics
• 作者: Donoso,LA;Shields,CL;Lee,EY
• 通讯作者: Lee,EY

A new perspective of S-antigen from immunochemical analysis.

免疫化学分析 S 抗原的新视角。

• DOI: 10.3109/02713689008999435
• 发表时间: 1990
• 期刊: Current eye research
• 影响因子: 2
• 作者: Gregerson,DS;Fling,SP;Obritsch,WF;Merryman,CF;Donoso,LA
• 通讯作者: Donoso,LA

Temporal analysis of retinal function in IRBP peptide-induced experimental autoimmune uveoretinitis (EAU).

IRBP 肽诱导的实验性自身免疫性葡萄膜视网膜炎 (EAU) 中视网膜功能的时间分析。

• 发表时间: 1990
• 期刊: Regional immunology
• 作者: Waldrep,JC;Ramanadham,S;Wood,JD;Donoso,LA
• 通讯作者: Donoso,LA

Identification of a uveitopathogenic and lymphocyte proliferation site in bovine S-antigen.

牛 S 抗原中葡萄膜致病位点和淋巴细胞增殖位点的鉴定。

• DOI: 10.1016/0008-8749(88)90193-1
• 发表时间: 1988
• 期刊: Cellular immunology
• 影响因子: 4.3
• 作者: Singh,VK;Nussenblatt,RB;Donoso,LA;Yamaki,K;Chan,CC;Shinohara,T
• 通讯作者: Shinohara,T