ANALYSIS OF T-CELL RECEPTOR-BETA-CHAINS IN LEWIS RATS WITH EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - CONSERVED COMPLEMENTARITY DETERMINING REGION-3
ANALYSIS OF T-CELL RECEPTOR-BETA-CHAINS IN LEWIS RATS WITH EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS - CONSERVED COMPLEMENTARITY DETERMINING REGION-3
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DOI：
10.1084/jem.174.6.1467
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发表时间：
1991-12-01
影响因子：
15.3
通讯作者：
WILSON, DB
中科院分区：
文献类型：
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作者：
GOLD, DP;OFFNER, H;WILSON, DB
本研究探讨T细胞抗原受体(TCR)β链元件在Lewis大鼠实验性变态反应性脑脊髓炎(EAE)中的应用。来自15个不同T细胞克隆和杂交瘤的TCR来自髓鞘碱性蛋白(MBP)免疫的动物，它们都对21聚体致脑片段MBP68-88具有特异性，利用V-β-8.2。此外，与V-β-8.2受体相关的连接互补决定区3(CDR3)的前两个氨基酸残基明显保守。15个中有12个含有天冬氨酸和丝氨酸，而不考虑相关的J-β元素。在核苷酸水平上，AspSer残基的这种保守是通过很少或不添加非Ermline编码的核苷酸(N)来完成的。在一些来自MBP免疫的淋巴结的V-beta-8.2分离株中也观察到了类似的AspSer使用和N区核苷酸增加的模式。相反，V-β-8.2聚合酶链式反应从刀豆蛋白A激活的Lewis T细胞或完全弗氏佐剂免疫动物的淋巴中分离到的分离株在CDR3中没有利用AspSer(0/31)，并且有4到9个N区核苷酸增加。根据这一发现，我们得出结论，CDR3中的AspSer残基，有限的N区核苷酸添加，以及V-β-8.2序列，有助于MBP68-88的TCR特异性。这增加了一种可能性，即导致脑部疾病的T细胞要么代表来自胎儿晚期的群体，要么是具有这种特定TCR表型的稀有细胞，在整个成年期对T细胞库做出贡献，并通过抗原进行选择。在任何一种情况下，CDR3 AspSer序列和V-β-8.2序列都是调节T细胞在恢复和抵抗活跃的EAE过程中识别的受体靶结构的候选序列。在这方面，对从活动的EAE动物中分离出来的针对MBP68-88的三个T细胞克隆的TCR利用的初步分析表明，虽然这三个克隆都使用V-β-8.2，但只有一个在CDR3中含有AspSer。
This study explores the usage of T cell antigen receptor (TCR) beta-chain elements in Lewis rats with experimentally induced allergic encephalomyelitis (EAE). TCRs from 15 different T cell clones and hybridomas derived from animals immunized with myelin basic protein (MBP), and all having specificity for the 21-mer encephalitogenic fragment MBP 68-88, utilized V-beta-8.2. In addition, there was a marked conservation of the first two amino acid residues of the junctional complementarily determining region 3 (CDR3) associated with the V-beta-8.2 receptors. 12 of 15 contained an aspartic acid followed by serine regardless of the associated J-beta element. At the nucleotide level, this conservation of AspSer residues was accomplished with few or no nongermline-encoded nucleotide (N) additions. A similar pattern of AspSer usage and N region nucleotide additions was observed in a number of V-beta-8.2 isolates derived from MBP-immunized lymph nodes. In contrast, V-beta-8.2 polymerase chain reaction amplified isolates from Lewis T cells activated with concanavalin A or from lymph nodes of complete Freund's adjuvant-immunized animals showed no AspSer utilization (0/31) in the CDR3, and four to nine N region nucleotide additions. We conclude from this finding that AspSer residues in the CDR3, limited N region nucleotide additions, along with V-beta-8.2 sequences, contribute to TCR specificity for MBP 68-88. This raises the possibility that encephalitogenic, disease-causing T cells either represent a population that derives from late fetal life or alternatively, that they are rare cells with this particular TCR phenotype contributed to the T cell pool throughout adulthood and are selected by antigen. In either case, the CDR3 AspSer sequences as well as V-beta-8.2 sequences are candidates for the receptor target structures recognized by regulator T cells in recovery from and resistance to active EAE. In this respect, a preliminary analysis of TCR utilization in three T cell clones specific for MBP 68-88 isolated from animals recovered from active EAE indicates that while all three use V-beta-8.2, only one contains AspSer in the CDR3.