title: Potential molecular mimicry between the human endogenous retrovirus W family envelope proteins and myelin proteins in multiple sclerosis.
abstract: Multiple sclerosis is an autoimmune disease caused by the destruction of the myelin sheath in the central nervous system. The major target molecules for the immune response are the myelin basic protein, myelin oligodendrocyte glycoprotein and proteolipid protein but the aetiology of the disease is as yet poorly understood. The HLA Class II allele DRB1*1501 in particular as well as DRB5*0101 and the expression of human endogenous retroviral envelope proteins have been linked to multiple sclerosis but the molecular mechanisms relating these remain to be elucidated. We hypothesised that cross-reactive peptide epitopes in retroviral envelope proteins and myelin proteins that can be presented by the two Class II DR molecules may play a role in initiating multiple sclerosis. Sequence homologies between retroviral envelope and myelin proteins and in silico predictions of peptides derived from them that are able to bind to the two Class II alleles were examined to test the hypothesis. The results support the hypothesis that molecular mimicry in peptide epitopes from envelope proteins of the HERV-W family of endogenous retroviruses and myelin proteins is possible and could potentially trigger multiple sclerosis. Mimicry between syncytin-1, a HERV-W envelope protein that is expressed during placentation, and myelin proteins may also explain the higher prevalence of multiple sclerosis in women. Experiments to test the ability of the identified peptide epitopes to activate THcells are required to confirm the present findings.
authors.affiliation: ID-FISH Technology Inc., 797 San Antonio Road, Palo Alto, CA 94303, United States. Electronic address: rjr200911@yahoo.com.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Ramasamy
authors.affiliation: Anglia Ruskin University, East Road, Cambridge CB1 1PT, United Kingdom.
authors.forename: Blessy
authors.initials: B
authors.lastname: Joseph
authors.affiliation: Department of Applied Sciences, University of West of England, Frenchay Campus, Bristol BS16 1QY, United Kingdom.
authors.forename: Trevor
authors.initials: T
authors.lastname: Whittall
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D020077:Endogenous Retroviruses / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015802:HLA-DR2 Antigen / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008297:Male; D018716:Molecular Mimicry; D009103:Multiple Sclerosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D004676:Myelin Basic Protein / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D009185:Myelin Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011257:Pregnancy Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015686:Gene Products, env; D015802:HLA-DR2 Antigen; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D011257:Pregnancy Proteins; D014759:Viral Envelope Proteins; C405335:syncytin
keywords: Autoimmunity; HLA DR2(15) haplotype; Human endogenous retroviruses; Molecular mimicry; Multiple sclerosis; Myelin proteins