Romagnoli P, Labhardt A M, Sinigaglia F
Pharma Research Technology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
EMBO J. 1991 Jun;10(6):1303-6. doi: 10.1002/j.1460-2075.1991.tb07648.x.
T cells generally recognize foreign antigens as peptides associated with self-molecules encoded by genes of the major histocompatibility complex (MHC). However, T cells which are specific for non-peptidic haptens have been described, in particular in patients with contact sensitivity reactions to metals such as nickel (Ni). Previously, we isolated MHC class II-restricted Ni-specific T cell clones from patients with Ni allergy. The experiments reported here examine the molecular basis for the interaction between Ni and peptide-MHC complexes. We find that Ni alters a T cell response to a peptide and show that Ni interacts with this peptide to alter its antigenicity rather than its ability to bind to MHC molecules. These findings hold implications for a model of hapten recognition by T cells.
T细胞通常将外来抗原识别为与主要组织相容性复合体(MHC)基因编码的自身分子相关的肽段。然而,已报道了对非肽类半抗原具有特异性的T细胞,特别是在对镍(Ni)等金属有接触性敏感反应的患者中。此前,我们从镍过敏患者中分离出了MHC II类限制性镍特异性T细胞克隆。本文报道的实验研究了镍与肽-MHC复合体之间相互作用的分子基础。我们发现镍改变了T细胞对肽的反应,并表明镍与该肽相互作用以改变其抗原性,而非其与MHC分子结合的能力。这些发现对T细胞对半抗原识别的模型具有启示意义。