Molecular mimicry and the autoimmune response to the peripheral nerve myelin PO glycoprotein |
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Authors: | Martin Adelmann Christopher Linington |
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Institution: | (1) Department of Neuroimmunology, Max-Planck-Institute of Psychiatry, Am Klopferspitz 18a, D-8033 Planegg-Martinsried, Germany |
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Abstract: | In the Lewis rat immunisation with the myelin PO glycoprotein can induce an inflammatory demyelinating disease of the peripheral nervous system, experimental allergic neuritis (EAN), which has many clinical and histopathological parallels with the human disease the Guillain-Barre syndrome. In view of the reported association of GBS with a number of infectious agents we have investigated whether molecular mimicry may occur between microbial antigens and the PO protein that could possibly trigger a similar pathogenic autoimmune response in man. A computer search of the available protein sequence data bases identified several absolute sequence homologies between PO and viral proteins that involve five or more consecutive amino acid residues. Four of these sequence homologies involved viral pathogens previously associated with the Guillain-Barre syndrome, namely Epstein-Barr virus (EBV), cytomegalovirus (CMV), Varicella zoster virus (VZV) and human immunodeficiency virus I (HIV I). Although, sequence homologies were also found between viral peptides and the neuritogenic determinants of PO, residues 56–71 and 180–199, these homologies proved incapable of eliciting EAN in the Lewis rat. These observations are discussed with reference to the role that molecular mimicry between T cell epitopes on pathogen derived antigens and the PO protein may play in the pathogenesis of the Guillain-Barre syndrome.Abbreviations EAN
Experimental allergic neuritis
- EAE
experimental allergic encephalomyelitis
- PNS
peripheral nervous system
- CNS
central nervous system
- MBP
myelin basic protein
- GBS
Guillain Barre syndrome
- CFA
complete Freund's Adjuvant
- LPC
lysophosphatidyl choline
- VZV
Varicella zoster virus
- CMV
cytomegalovirus
- EBV
Epstein Barr virus
- HIV I
human immunodeficiency virus I
Special issue dedicated to Dr. Alan N. Davison |
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Keywords: | Experimental allergic neuritis Guillain-Barre syndrome myelin PO glycoprotein molecular mimicry Varicella zoster virus cytomegalovirus Epstein Barr virus |
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