Offner H, Hashim G A, Vandenbark A A
V.A. Medical Center, Portland, OR 97201.
Regul Pept. 1994 May 5;51(2):77-90. doi: 10.1016/0167-0115(94)90197-x.
In this review, we describe an anti-idiotypic regulatory mechanism that is naturally induced by the autoimmune disease process, and that can be boosted by injection of TCR peptides that mimic epitopes generated naturally from germline sequences. The striking similarities in the induction and characteristics of rodent and human T cells specific for TCR peptides support the generality of the observation, and enhance the probability that this immunoregulatory mechanism will have application in human organ-specific autoimmune diseases that are characterized by oligoclonal expression of TCR V genes. The major challenges that remain to be resolved to make the TCR peptide therapy more widely applicable include (1) establishing disease-relevant V gene biases in individual patients, (2) identifying biologically active TCR peptide sequences, and (3) demonstrating that the induction of anti-TCR peptide immunity in humans can reduce the pernicious activity of autoreactive T cells putatively directed at organ-specific target antigens.
在本综述中，我们描述了一种由自身免疫疾病过程自然诱导的抗独特型调节机制，并且通过注射模拟从种系序列自然产生的表位的TCR肽可以增强这种机制。啮齿动物和人类针对TCR肽的T细胞在诱导和特性方面的显著相似性支持了这一观察结果的普遍性，并增加了这种免疫调节机制将应用于以TCR V基因寡克隆表达为特征的人类器官特异性自身免疫疾病的可能性。为使TCR肽疗法更广泛适用而仍有待解决的主要挑战包括：（1）在个体患者中确定与疾病相关的V基因偏向性；（2）鉴定具有生物活性的TCR肽序列；（3）证明在人类中诱导抗TCR肽免疫能够降低假定针对器官特异性靶抗原的自身反应性T细胞的有害活性。
