Differential induction of experimental autoimmune encephalomyelitis by myelin basic protein molecular mimics in mice humanized for HLA-DR2 and an MBP(85-99)-specific T cell receptor.
Multiple sclerosis (MS) is a chronic autoimmune neurological disease characterized by infiltration of peripheral inflammatory cells to the central nervous system (CNS) and demyelination of CNS white matter. Epidemiological evidence suggests a possible infectious trigger. One potential mechanism by which an infectious agent may trigger MS is via molecular mimicry wherein T cells generated against foreign epitopes cross-react with self-myelin epitopes, such as myelin basic protein (MBP), with sufficient sequence similarity. It has been previously reported that an MBP(85-99)-reactive T cell clone derived from an MS patient cross-reacted with multiple bacterial-derived mimic peptides in vitro. We show that the same mimic peptides can induce clinical disease in two different strains of mice transgenic for both a human MBP(85-99)-specific TCR and HLA-DR2 (MHC II), albeit with different disease patterns - relapsing-remitting vs. monophasic. Interestingly, clinical disease correlates with CNS infiltration of CD4(+) T cells and F4/80(+) macrophages, but not with in vitro proliferative or cytokine responses of splenocytes in response to either MBP(85-99) or its mimics.
Greene
Maria T
MT
Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, United States.
Ercolini
Anne M
AM
DeGutes
Mathew
M
Miller
Stephen D
SD
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015802:HLA-DR2 Antigen / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018716:Molecular Mimicry / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte; D015802:HLA-DR2 Antigen; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; C107908:myelin basic protein 85-99