Differential induction of experimental autoimmune encephalomyelitis by myelin basic protein molecular mimics in mice humanized for HLA-DR2 and an MBP85–99 -specific T cell receptor

• Published in: Journal of autoimmunity Vol. 31; no. 4; pp. 399 - 407
• Main Authors: Greene, Maria T, Ercolini, Anne M, DeGutes, Mathew, Miller, Stephen D
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier 01.12.2008
• Subjects: Allergy and Immunology; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Medical sciences; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Autoimmunity; PBS; complete Freund's adjuvant; Multiple sclerosis; TCR; proteolipid protein; T cell receptor; MS; Transgenic mice; Experimental autoimmune encephalomyelitis; EAE; CNS; lumbar spinal cord; phosphate-buffered saline; T cells; Myelin basic protein; cerebellum; central nervous system; PLP; Molecular mimicry; MBP; LSC; CFA; Cb; Animal model; HLA-System; Major histocompatibility system; Transgenic animal; Autoimmune disease; Inflammatory disease; Immunology; Basic protein; T-Lymphocyte; Class I histocompatibility antigen; Immunopathology; Nervous system diseases; Induction; Myelin; Rodentia; Experimental allergic encephalomyelitis; Vertebrata; Mammalia; Mouse; Central nervous system disease
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2008.09.004

Abstract 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 MBP85–99 -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 MBP85–99 -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 MBP85–99 or its mimics.