Autoantibodies that recognize functional domains of hnRNPA1 implicate molecular mimicry in the pathogenesis of neurological disease

被引:26
作者
Lee, Sang Min
Dunnavant, Floyd D.
Jang, Haeman
Zunt, Joseph
Levin, Michael C.
机构
[1] Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN 38163 USA
[2] Vet Affairs Med Ctr, Res Serv, Memphis, TN USA
[3] Univ Tennessee, Hlth Sci Ctr, Ctr Neurobiol Brain Dis, Memphis, TN USA
[4] Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN USA
[5] Univ Tennessee, Hlth Sci Ctr, Ctr Excellence Connect Tissue Dis, Memphis, TN USA
[6] Univ Washington, Dept Neurol, Seattle, WA USA
关键词
human T lymphotropic virus type 1; heterogeneous nuclear ribonucleoprotein A1; neurologic; HTLV-1 associated myelopathy/tropical spastic paraparesis; multiple sclerosis; autoimmune;
D O I
10.1016/j.neulet.2006.03.016
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
As a model for molecular mimicry in neurological disease, we study people infected with human T lymphotropic virus type 1 (HTLV-1) who develop HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), an immune-mediated disease of the central nervous system (CNS). In HAM/TSP, data suggests molecular mimicry is the result of cross-reactive antibodies between HTLV-1-tax and heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), a protein over-expressed in human CNS neurons. The hnRNP A1 epitope recognized by autoantibodies was unknown. In this study, we hypothesized that antibodies purified from HAM/TSP patients would react with functionally significant domains of hnRNP A1. Western blotting of functionally significant deletion mutants and overlapping fusion proteins using HAM/TSP IgG revealed two core epitopes within the C-terminal region of hnRNP A1. The first (aminoacids 191-SSQRGRSGSGNF-202), overlapped the RGG domain and the second (aminoacids 293-GQYFAKPRNQGG-304), with the M9 shuttling sequence, two functionally important regions of hnRNP A1. Monoclonal antibodies to HTLV-1-tax also reacted with the epitopes. These data fulfill an important criterion of molecular mimicry, namely that mimicking epitopes are not random, but include biologically significant regions of target proteins. This suggests an important role for the cross-reactive immune response between HTLV-1 and hnRNP A1 in the pathogenesis of immune-mediated neurological diseases via molecular mimicry. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:188 / 193
页数:6
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