Cross-reactivity between immunodominant human T lymphotropic virus type I tax and neurons: implications for molecular mimicry.
Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is associated with immunoreactivity to HTLV-I tax. Antibodies isolated from patients with HAM/TSP and monoclonal antibodies (MAbs) to HTLV-I tax stained neurons. In neuronal extracts, HAM/TSP immunoglobulin G identified heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) as the autoantigen. Importantly, tax MAbs reacted with hnRNP A1. To identify the epitope recognized by the tax MAbs, the fine epitope specificity of the antibodies was determined using overlapping peptides. This analysis identified an epitope at the C-terminus (tax(346-353)), which overlaps a human immunodominant domain. Preincubation of this peptide with tax MAbs inhibited antibody binding to tax, hnRNP A1, and neurons. This indicates that a cross-reactive immune response between HTLV-I tax and neuronal hnRNP A1 is contained within the human immunodominant epitope of tax and suggests that molecular mimicry plays a role in the pathogenesis of HAM/TSP.
Levin
Michael C
MC
Research Division, Veterans Affairs Medical Center-Memphis, and Laboratory of Viral and Demyelinating Diseases, Department of Neurology, University of Tennessee, Memphis, Tenneesse 38163, USA. mlevin@utmem.edu
Lee
Sang Min
SM
Morcos
Yvette
Y
Brady
John
J
Stuart
John
J
D003429:Cross Reactions; D016356:Gene Products, tax / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes; D018716:Molecular Mimicry; D009474:Neurons / Q000276:immunology*
D016356:Gene Products, tax; D016056:Immunodominant Epitopes