A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H‐2^b mice: Fine specificity and T cell receptor Vβ expression of encephalitogenic T cells

Abstract

A predominant response to myelin oligodendrocyte glycoprotein (MOG) was recently observed in patients with multiple sclerosis (MS). To study the possible pathogenic role of T cell response to MOG in MS, we have investigated the encephalitogenic potential of MOG. Synthetic MOG peptides, pMOG 1-21, 35-55, 67-87, 104-117 and 202-218, representing predicted T cell epitopes, were injected into C57BL/6J and C3H.SW (H-2b) mice. The mice developed significant specific T cell responses to pMOG 1-21, pMOG 35-55 and pMOG 104-117. However, pMOG 35-55 was the only MOG peptide which could induce neurological impairment. The highly reproducible disease was chronic, with ascending paralysis and neuropathology comparable with those observed in experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein or proteolipid protein, except that in H-2b mice the disease was consistently non-remitting. These features differ markedly from those which we recently observed in PL (H-2u) mice with pMOG 35-55-induced disease. In PL mice, pMOG 35-55-induces atypical chronic relapsing EAE, the expression and progression of which are unpredictable. Hence, in different mouse strains, the same MOG peptide can induce typical EAE characterized by ascending paralysis, or atypical EAE with unpredictable clinical signs. pMOG 35-55-specific T cells from H-2b mice recognized an epitope within amino acids 40-55 of the MOG molecule, and pMOG 40-55-reactive T cell lines were encephalitogenic upon transfer into syngeneic recipients. The encephalitogenic pMOG 35-55-reactive C57BL/6J T cell lines expressed V beta 1, V beta 6, V beta 8, V beta 14 and V beta 15 gene segments, and the pMOG 35-55-reactive C3H.SW T cell lines expressed V beta 1, V beta 2, V beta 6, V beta 8, V beta 10, V beta 14, and V beta 15 gene segments. However, in both mouse strains, the utilization of the V beta 8 gene product was predominant (40-43%). The highly reproducible encephalitogenic activity of pMOG 35-55 strongly suggests a pathogenic role for T cell reactivity to MOG in MS and supports the possibility that MOG may also be a primary target antigen in the disease.

Obesity predisposes to Th17 bias

“…As is well established [9,10], frequencies of Th17 cells were small and we therefore determined whether this Th17 sublineage bias is maintained during active T-cell priming and expansion. We measured Th17 and Th1 cell populations in draining lymph nodes following immunization of DIO and RD mice with a well-characterized H-2 b -binding peptide, myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) [11]. Six days after immunization, lymphocytes from draining lymph nodes of DIO donors generated a dramatically increased pool size of CD4 1 IL-17 1 cells, compared with lymph node cells from RD mice (Fig.…”

Anatomy of T cell autoimmunity to myelin oligodendrocyte glycoprotein (MOG): Prime role of MOG44F in selection and control of MOG‐reactive T cells in H‐2b mice

“…The majority of the clones (clones 3, 5, 6, 3a, 4a, 5a, 10a, 12a, 14a and 15a) expressed Vb8, an observation on par with the predominant expression of Vb8 by MOG35-55-specific T cell lines from H-2 b mice (48%; [8,9]). Some of these Vb8 + T cell clones, however, seem clonally heterogenic due to their variable co-expression of Va gene segments.…”

“…Although the encephalitogenic potential of MOG has been demonstrated in several mouse strains [8][9][10][11], rats [12], marmosets [13,14] and rhesus monkeys [15], and T/B cell autoreactivity against MOG has been suggested to play an important role in the pathogenesis of MS [16][17][18][19], the MOG-induced potentially pathogenic T cells have not been fully characterized. Our partial characterization of MOG-reactive T cells has indicated that the now widely used model of MOG-induced EAE in H-2 b mice [8,9] is mediated by TCR-heterogeneous T cells reactive against the single immunodominant encephalitogenic epitope MOG35-55, and our work defined MOG37-52 as the minimal sequence optimally stimulating encephalitogenic MOG35-55-specific line T cells [8,9]. In this study, the pathogenic T cell autoreactivity associated with MOG-induced EAE in H-2 b mice was dissected at the clonal level.…”

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

“…Three major myelin antigens or their peptides have been found to induce EAE in rodent or non-rodent species. These are myelin basic protein (MBP) (Zamvil et al, 1986), myelin oligodendrocyte glycoprotein (MOG) (Mendel et al, 1995), and proteolipid protein (PLP) (Tuohy et al, 1989). The microbial mimics capable of inducing EAE have been reported for all the above except for PLP.…”