HTLV-1 induced molecular mimicry in neurological disease.
As a model for molecular mimicry, we study patients infected with human T-lymphotropic virus type 1 (HTLV-1) who develop a neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease with important biological similarities to multiple sclerosis (MS) (Khan et al. 2001; Levin et al. 1998, 2002a; Levin and Jacobson 1997). The study of HAM/TSP, a disease associated with a known environmental agent (HTLV-1), allows for the direct comparison of the infecting agent with host antigens. Neurological disease in HAM/TSP patients is associated with immune responses to HTLV-1-tax (a regulatory and immunodominant protein) and human histocompatibility leukocyte antigen (HLA) DRB1*0101 (Bangham 2000; Jacobson et al. 1990; Jeffery et al. 1999; Lal 1996). Recently, we showed that HAM/TSP patients make antibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), a neuron-specific autoantigen (Levin et al. 2002a). Monoclonal antibodies to tax cross-reacted with hnRNP A1, indicating molecular mimicry between the two proteins. Infusion of cross-reactive antibodies with an ex vivo system completely inhibited neuronal firing indicative of their pathogenic nature (Kalume et al. 2004; Levin et al. 2002a). These data demonstrate a clear link between chronic viral infection and autoimmune disease of the central nervous system (CNS) in humans and, we believe, in turn will give insight into the pathogenesis of MS.
Lee
S M
SM
Department of Neurology, University of Tennessee Health Sciences Center, Memphis 38163, USA.
Morcos
Y
Y
Jang
H
H
Stuart
J M
JM
Levin
M C
MC
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D001921:Brain / Q000276:immunology / Q000503:physiopathology; D003429:Cross Reactions; D016356:Gene Products, tax / Q000276:immunology; D015234:HLA-A Antigens; D059811:HLA-DRB1 Chains; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D018448:Models, Immunological; D018716:Molecular Mimicry / Q000276:immunology*; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology; D015493:Paraparesis, Tropical Spastic / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D016356:Gene Products, tax; D015234:HLA-A Antigens; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B