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HLA II类基因与多发性硬化易感性关联的功能基础:一个多重家庭中针对髓鞘碱性蛋白的细胞免疫反应

A functional basis for the association of HLA class II genes and susceptibility to multiple sclerosis: cellular immune responses to myelin basic protein in a multiplex family.

作者信息

Voskuhl R R, Martin R, McFarland H F

机构信息

Neuroimmunology Branch, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

出版信息

J Neuroimmunol. 1993 Feb;42(2):199-207. doi: 10.1016/0165-5728(93)90011-m.

DOI:10.1016/0165-5728(93)90011-m
PMID:7679119
Abstract

This study has examined the cellular response to myelin basic protein (MBP) in a multiplex family with multiple sclerosis (MS). A total of 81 MBP-specific T cell lines (TCLs) were derived from three affected siblings and four healthy siblings. No difference was observed in estimated precursor frequencies of MBP-specific TCLs or peptide specificity of TCLs when comparing affected and unaffected siblings. MBP-specific TCLs from affected siblings, however, were restricted to the DRw15/DQw6 allele more frequently than those from unaffected siblings (P < 0.02). These data suggest that restriction of autoantigen-specific T cells may be the functional basis for disease susceptibility related to HLA class II inheritance.

摘要

本研究检测了一个患有多发性硬化症(MS)的多重家庭中细胞对髓鞘碱性蛋白(MBP)的反应。共从三名患病兄弟姐妹和四名健康兄弟姐妹中获得了81个MBP特异性T细胞系(TCL)。比较患病和未患病的兄弟姐妹时,未观察到MBP特异性TCL的估计前体频率或TCL的肽特异性存在差异。然而,与未患病兄弟姐妹的MBP特异性TCL相比,患病兄弟姐妹的MBP特异性TCL更频繁地受限 于DRw15/DQw6等位基因(P < 0.02)。这些数据表明,自身抗原特异性T细胞的受限可能是与HLA II类遗传相关的疾病易感性的功能基础。

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A functional basis for the association of HLA class II genes and susceptibility to multiple sclerosis: cellular immune responses to myelin basic protein in a multiplex family.HLA II类基因与多发性硬化易感性关联的功能基础:一个多重家庭中针对髓鞘碱性蛋白的细胞免疫反应
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引用本文的文献

1
Regulation of interleukin (IL)-12 receptor beta2 subunit expression by endogenous IL-12: a critical step in the differentiation of pathogenic autoreactive T cells.内源性白细胞介素(IL)-12对IL-12受体β2亚基表达的调控:致病性自身反应性T细胞分化的关键步骤。
J Exp Med. 1999 Mar 15;189(6):969-78. doi: 10.1084/jem.189.6.969.
2
Immunodominance of a low-affinity major histocompatibility complex-binding myelin basic protein epitope (residues 111-129) in HLA-DR4 (B1*0401) subjects is associated with a restricted T cell receptor repertoire.在HLA - DR4(B1*0401)受试者中,低亲和力的主要组织相容性复合体结合髓鞘碱性蛋白表位(第111 - 129位氨基酸残基)的免疫显性与受限的T细胞受体库相关。
J Clin Invest. 1997 Jul 15;100(2):339-49. doi: 10.1172/JCI119539.
3
A novel candidate autoantigen in a multiplex family with multiple sclerosis: prevalence of T-lymphocytes specific for an MBP epitope unique to myelination.一个患有多发性硬化症的复合家庭中的新型候选自身抗原:针对髓鞘形成特有的髓鞘碱性蛋白(MBP)表位的T淋巴细胞患病率。
J Neuroimmunol. 1993 Jul;46(1-2):137-44. doi: 10.1016/0165-5728(93)90243-r.