Bourdette D N, Whitham R H, Chou Y K, Morrison W J, Atherton J, Kenny C, Liefeld D, Hashim G A, Offner H, Vandenbark A A
Veterans Affairs Medical Center, Portland, OR 97201.
J Immunol. 1994 Mar 1;152(5):2510-9.
Immunization with disease-associated TCR V region peptides is an effective treatment for experimental autoimmune encephalomyelitis. Myelin basic protein-specific T cells, which induce experimental autoimmune encephalomyelitis in many animal strains, may be important in the pathogenesis of multiple sclerosis. Myelin basic protein-specific T cell clones from some multiple sclerosis patients preferentially use TCR V genes from the V beta 5.2 and V beta 6.1 families. To assess the safety and immunogenicity of TCR V beta 5.2 and V beta 6.1 peptides, we injected 11 multiple sclerosis patients with varying doses of two synthetic peptides, TCR V beta 5.2(39-59) and V beta 6.1(39-59), encompassing the CDR2 region of these V gene families. Low doses (100 to 300 micrograms) of peptide induced T cell immunity in 7 of 11 patients to one or both peptides. Delayed type hypersensitivity skin responses to the peptides were observed in three of seven responders, and TCR peptide-specific Ab occurred in two of seven T cell responders. Low doses of TCR peptides produced no side effects and did not cause broad spectrum immunosuppression. Synthetic TCR V region peptides can induce T cell immunity safely in humans and may prove useful in treating human autoimmune diseases.
用疾病相关的TCR V区肽进行免疫是治疗实验性自身免疫性脑脊髓炎的有效方法。髓鞘碱性蛋白特异性T细胞在许多动物品系中可诱发实验性自身免疫性脑脊髓炎，可能在多发性硬化症的发病机制中起重要作用。一些多发性硬化症患者的髓鞘碱性蛋白特异性T细胞克隆优先使用Vβ5.2和Vβ6.1家族的TCR V基因。为评估TCR Vβ5.2和Vβ6.1肽的安全性和免疫原性，我们给11例多发性硬化症患者注射了不同剂量的两种合成肽，即TCR Vβ5.2(39 - 59)和Vβ6.1(39 - 59)，它们涵盖了这些V基因家族的互补决定区2（CDR2）区域。低剂量（100至300微克）的肽在11例患者中的7例中诱导了针对一种或两种肽的T细胞免疫。在7名有反应者中的3名中观察到对肽的迟发型超敏皮肤反应，在7名T细胞反应者中的2名中出现了TCR肽特异性抗体。低剂量的TCR肽未产生副作用，也未引起广谱免疫抑制。合成的TCR V区肽可在人体中安全地诱导T细胞免疫，可能对治疗人类自身免疫性疾病有用。
