Targoni O S, Lehmann P V
Institute of Pathology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
J Exp Med. 1998 Jun 15;187(12):2055-63. doi: 10.1084/jem.187.12.2055.
To study the contribution of endogenous myelin basic protein (MBP) to the positive and/or negative selection of the MBP-specific T cell repertoire, we studied the T cell response to MBP in MBP-deficient shiverer and MBP-expressing congenic C3H mice. Immunization with MBP induced a vigorous T cell response in shiverer mice directed against a single I-Ak- restricted immunodominant determinant, the core of which is peptide MBP:79-87 (DENPVVHFF). Injection of this peptide induced a high avidity T cell repertoire in shiverer mice that primarily consisted of clones capable of recognizing the native MBP protein in addition to the peptide itself. These data show that endogenous MBP is not required for the positive selection of an MBP-specific T cell repertoire. C3H mice, in contrast, were selectively unresponsive to the MBP protein and injection of MBP:79-87 peptide induced a low avidity repertoire that could be stimulated only by the peptide, not by the protein. Therefore, endogenous MBP induced profound inactivation of high avidity clones specific for the immunodominant determinant making that determinant appear cryptic.
为了研究内源性髓鞘碱性蛋白（MBP）对MBP特异性T细胞库阳性和/或阴性选择的作用，我们研究了MBP缺陷的颤抖小鼠和表达MBP的同基因C3H小鼠对MBP的T细胞反应。用MBP免疫在颤抖小鼠中诱导了针对单一I-Ak限制性免疫显性决定簇的强烈T细胞反应，其核心是肽MBP:79-87（DENPVVHFF）。注射该肽在颤抖小鼠中诱导了高亲和力T细胞库，该库主要由除了肽本身之外还能够识别天然MBP蛋白的克隆组成。这些数据表明，MBP特异性T细胞库的阳性选择不需要内源性MBP。相比之下，C3H小鼠对MBP蛋白选择性无反应，注射MBP:79-87肽诱导了低亲和力库，该库只能被肽刺激，而不能被蛋白刺激。因此，内源性MBP导致对免疫显性决定簇特异的高亲和力克隆的深度失活，使得该决定簇显得隐蔽。
