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Autoantibodies that recognize functional domains of hnRNPA1 implicate molecular mimicry in the pathogenesis of neurological disease
- Source :
- Neuroscience Letters. 401:188-193
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- 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.
- Subjects :
- medicine.drug_class
Heterogeneous Nuclear Ribonucleoprotein A1
Recombinant Fusion Proteins
viruses
Cross Reactions
Biology
Monoclonal antibody
medicine.disease_cause
Article
Epitope
Pathogenesis
Epitopes
immune system diseases
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Tropical spastic paraparesis
medicine
Humans
Autoantibodies
Neurons
General Neuroscience
Molecular Mimicry
virus diseases
medicine.disease
HTLV-I Infections
Virology
Fusion protein
Paraparesis, Tropical Spastic
Protein Structure, Tertiary
Cell biology
Molecular mimicry
Spinal Cord
Immunoglobulin G
Mutation
biology.protein
Antibody
Subjects
Details
- ISSN :
- 03043940
- Volume :
- 401
- Database :
- OpenAIRE
- Journal :
- Neuroscience Letters
- Accession number :
- edsair.doi.dedup.....9530eba4d3b40a6dcc1b49da0f417593