Post-translational glycosylation of target proteins implicate molecular mimicry in the pathogenesis of HTLV-1 associated neurological disease.
We hypothesized that molecular mimics between human T lymphotropic virus type 1 (HTLV-1) and human autoantigens were based upon post-translational modification of target proteins. Proteins purified from MT-2 (HTLV-1 infected) and Jurkat (HTLV-1 negative) cells were used for western blotting with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) IgG. In contrast to normal IgG, HAM/TSP IgG immunoreacted with proteins in MT-2 cells at 22-24 kDa, pI 8.0, which were identified as peroxiredoxin 1 and HTLV-1-p24-(gag) by mass spectroscopy. Western blots following glycoprotein purification showed that HAM/TSP IgG reacted with PrX-1 and p24 in MT-2 cells but not in Jurkat cells, indicating that the mimicking target proteins were glycosylated. These data suggest that post-translational glycosylation of target proteins may play a role in the pathogenesis of HAM/TSP.
Lee
Sangmin
S
Research Service, Veterans Affairs Medical Center, Memphis, TN, USA.
Shin
Yoojin
Y
Marler
Jacob
J
Levin
Michael C
MC
D002478:Cells, Cultured; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D015490:HTLV-I Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D019169:Jurkat Cells; D018716:Molecular Mimicry / Q000276:immunology*; D009422:Nervous System Diseases / Q000209:etiology / Q000276:immunology* / Q000821:virology*; D054464:Peroxiredoxins / Q000276:immunology / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism / Q000648:ultrastructure
D006023:Glycoproteins; D007074:Immunoglobulin G; D015682:Retroviridae Proteins, Oncogenic; C060954:p24 protein, Human T-lymphotropic virus 1; C515940:PRDX1 protein, human; D054464:Peroxiredoxins