In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis.
A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MBP(87-99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Barr virus (EBV). These low dose viral peptide- specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide-specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide-specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.
Ufret-Vincenty
R L
RL
Neurological Diseases Section, Neuroimmunology Branch, Bethesda, Maryland 20892, USA.
Quigley
L
L
Tresser
N
N
Pak
S H
SH
Gado
A
A
Hausmann
S
S
Wucherpfennig
K W
KW
Brocke
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001324:Autoantigens; D002470:Cell Survival; D003429:Cross Reactions; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D001324:Autoantigens; D004676:Myelin Basic Protein; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; C115314:myelin basic protein 87-99