Hin S, Zabel C, Bianco A, Jung G, Walden P
Department of Dermatology, Medical Faculty Charité, Humboldt University, Berlin, Germany.
J Immunol. 1999 Sep 1;163(5):2363-7.
TCR antagonists are altered T cell epitopes that specifically inactivate T cells. Commonly, they are derived from agonists by amino acid side chain replacement at positions accessible to the TCR. In this paper we report for the first time that a main chain N-hydroxylation, which is not exposed at the surface of the MHC peptide complex, renders an agonist into an antagonist. These mimotopes are a new, yet undescribed class of TCR antagonists. The antagonists are about 100 times more potent than an unrelated peptide that competes for binding to the MHC molecule. The novel main chain modification enhances biostability and maintains side chain constitution and thus opens new prospects for the use of TCR antagonists in the treatment of pathological immune reactions.
TCR拮抗剂是经过改变的T细胞表位，可特异性使T细胞失活。通常，它们是通过在TCR可及位置进行氨基酸侧链替换，从激动剂衍生而来。在本文中，我们首次报道，一种未暴露于MHC肽复合物表面的主链N-羟基化作用，可将激动剂转变为拮抗剂。这些模拟表位是一类新的、尚未被描述的TCR拮抗剂。这些拮抗剂的效力比一种竞争结合MHC分子的不相关肽强约100倍。这种新的主链修饰增强了生物稳定性并维持了侧链结构，从而为TCR拮抗剂在治疗病理性免疫反应中的应用开辟了新前景。
