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正常T细胞系对从正常和多发性硬化症白质中分离出的髓鞘碱性蛋白的反应性。

Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter.

作者信息

McLaurin J A, Hafler D A, Antel J P

机构信息

Montreal Neurological Institute, Department of Neuroimmunology, Quebec, Canada.

出版信息

J Neurol Sci. 1995 Feb;128(2):205-11. doi: 10.1016/0022-510x(94)00224-c.

Abstract

T-cell reactivity to human myelin basic protein (MBP) has been extensively studied using T-cell lines and clones generated from both peripheral blood and cerebrospinal fluid, from normal controls and multiple sclerosis (MS) patients. These studies have largely utilized myelin basic protein isolated from control human adult white matter. In our study, we used MBP reactive T-cell lines as a probe to investigate antigenic differences in a series of MBP preparations isolated from either control human white matter or white matter from the central nervous system (CNS) of MS patients. Autologous peripheral blood derived mononuclear cells were used as antigen presenting cells (APC). Although the majority of T-cells were found to react equally well with all preparations of MBP isolated from both control and MS white matter, we were also able to identify T-cell lines which reacted well with all preparations of MBP isolated from controls but failed to react with MBP isolated from MS white matter. These differences were unlikely to reflect differences in degradation products or excess peptides present in the MS brain since SDS-PAGE and HPLC did not show any difference in the MS samples compared to the controls, and the concentration response curves for a human T-cell clone specific for the 84-102 region of MBP were similar for all the MBP preparations. We did not detect differences in amino acid content amongst MBP preparations although single amino acid substitutions cannot be ruled out. These results raise the possibility that MBP isolated from MS brain may differ in charge microheterogeneity which would affect antigenic determinants.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

利用从正常对照和多发性硬化症(MS)患者的外周血和脑脊液中产生的T细胞系和克隆,对T细胞与人髓鞘碱性蛋白(MBP)的反应性进行了广泛研究。这些研究大多使用从对照成人人类白质中分离的髓鞘碱性蛋白。在我们的研究中,我们使用MBP反应性T细胞系作为探针,来研究从对照人类白质或MS患者中枢神经系统(CNS)白质中分离的一系列MBP制剂中的抗原差异。自体外周血来源的单核细胞用作抗原呈递细胞(APC)。虽然发现大多数T细胞与从对照和MS白质中分离的所有MBP制剂反应同样良好,但我们也能够鉴定出与从对照中分离的所有MBP制剂反应良好但与从MS白质中分离的MBP不反应的T细胞系。这些差异不太可能反映MS脑内降解产物或过量肽的差异,因为与对照相比,SDS-PAGE和HPLC在MS样品中未显示任何差异,并且针对MBP 84-102区域的人T细胞克隆的浓度反应曲线在所有MBP制剂中相似。尽管不能排除单个氨基酸替换,但我们未检测到MBP制剂之间氨基酸含量的差异。这些结果增加了从MS脑分离的MBP在电荷微不均一性方面可能存在差异的可能性,这会影响抗原决定簇。(摘要截短于250字)

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