IDENTIFICATION OF T-CELL RECOGNITION SITES IN S-ANTIGEN - DISSOCIATION OF PROLIFERATIVE AND PATHOGENIC SITES
IDENTIFICATION OF T-CELL RECOGNITION SITES IN S-ANTIGEN - DISSOCIATION OF PROLIFERATIVE AND PATHOGENIC SITES
复制标题
DOI：
10.1016/0008-8749(89)90302-x
复制
发表时间：
1989-10-15
影响因子：
4.3
通讯作者：
DONOSO, LA
中科院分区：
文献类型：
--
作者：
GREGERSON, DS;FLING, SP;DONOSO, LA
实验性自身免疫性葡萄膜视网膜炎（EAU）是一种主要由CD 4 + T细胞介导的视网膜、眼葡萄膜和松果体的自身免疫性炎症性疾病。S抗原是一种存在于视网膜感光细胞和松果体细胞中的蛋白质，是诱导易感物种和品系中EAU的有效试剂。为了确定S抗原的T细胞识别位点，负责其葡萄膜致敏性和增殖反应，溴化氰（CB）片段以及合成的肽被用来测试两个葡萄膜致敏T细胞系，R9和R17，分别针对天然牛和人S抗原制备的增殖反应。已知两种非重叠的合成肽（牛序列的氨基酸残基286-297和303-314）可积极诱导EAU，但在任一S抗原特异性T细胞系中均不能诱导增殖反应。然而，这两个位点分别与合成肽残基273-292和317-328相邻，它们不能积极诱导EAU，但引起了牛和人S抗原诱导的T细胞系的强烈增殖反应。用含有这些增殖位点之一（残基317-328）的合成肽重复体外选择R9 T细胞系，产生了瞬时葡萄膜原性T细胞系。几个物种特异性T细胞表位被确定，但没有发现这些参与葡萄膜反应。我们的研究结果表明，空间上分离和不同的T细胞表位存在于S-抗原，这是负责主动诱导EAU，淋巴细胞增殖，并过继转移EAU的能力。
Experimental autoimmune uveoretinitis (EAU) is a predominantly CD4+ T cell-mediated autoimmune inflammatory disease of the retina and uveal tract of the eye and the pineal gland. S-antigen, a protein found in retinal photoreceptor cells and pinealocytes, is a potent agent for the induction of EAU in susceptible species and strains. In order to identify the T cell recognition sites of S-antigen responsible for its uveitogenicity and proliferative responses, cyanogen bromide (CB) fragments as well as synthetic peptides were used to test the proliferative responses of two uveitogenic T cell lines, R9 and R17, prepared against native bovine and human S-antigen, respectively. Two nonoverlapping synthetic peptides which are known to actively induce EAU, amino acid residues 286-297 and 303-314 of the bovine sequence, were unable to induce proliferative responses in either S-antigen-specific T cell line. However, both of these sites were adjacent to synthetic peptides, residues 273-292 and 317-328, respectively, which wre unable to actively induce EAU, but elicited strong proliferative responses from T cell lines raised to bovine and human S-antigen. Repeated in vitro selection of the R9 T cell line with asynthetic peptide containing one of these proliferative sites, residues 317-328, gave rise to a transiently uveitogenic T cell line. Several species-specific T cell epitopes were identified, but none of these were found to be involved in a uveitogenic response. Our results indicate that spatially separated and distinct T cell epitopes are present in S-antigen which are responsible for the active induction of EAU, lymphocyte proliferation, and the ability to adoptively transfer EAU.