Myelin/Oligodendrocyte Glycoprotein-Induced Autoimmune Encephalomyelitis in Common Marmosets: The Encephalitogenic T Cell Epitope pMOG24–36 Is Presented by a Monomorphic MHC Class II Molecule

Abstract

Immunization of common marmosets (Callithrix jacchus) with a single dose of human myelin in CFA, without administration of Bordetella pertussis, induces a form of autoimmune encephalomyelitis (EAE) resembling in its clinical and pathological expression multiple sclerosis in humans. The EAE incidence in our outbred marmoset colony is 100%. This study was undertaken to assess the genetic and immunological basis of the high EAE susceptibility. To this end, we determined the separate contributions of immune reactions to myelin/oligodendrocyte glycoprotein (MOG) and myelin basic protein to the EAE induction. Essentially all pathological features of myelin-induced EAE were also found in animals immunized with MOG in CFA, whereas in animals immunized with myelin basic protein in CFA clinical and pathological signs of EAE were lacking. The epitope recognition by anti-MOG Abs and T cells were assessed. Evidence is provided that the initiation of EAE is based on T and B cell activation by the encephalitogenic phMOG14–36 peptide in the context of monomorphic Caja-DRB*W1201 molecules.

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

“…Deep CLN were also isolated from common marmoset monkeys (Callithrix jacchus) during chronic EAE (n=5) [25,26]. Control CLN were from marmosets (n=2) immunized with ovalbumin in complete Freund's adjuvant (CFA) [21].…”

Quantitative MRI‐pathology correlations of brain white matter lesions developing in a non‐human primate model of multiple sclerosis

“…The animals were immunized with 100 mg rhMOG emulsified in CFA into the dorsal skin at four locations, two in the axillary and two in the ingional region (4). EAE scoring.…”

“…Owing to the sharing of the MHC class II allele Caja-DRB Ã W 12 0 1 , 100% of monkeys are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE), a widely accepted experimental model of the chronic inflammatory disease multiple sclerosis (MS) (3,4). The marmoset thus provides a useful preclinical model for basic research and for the efficacy testing of new therapies that fail to work in animal models more distinct from humans, such as rats and mice.…”

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

“…Of these, only autoreactivities associated with MBP-and PLPinduced EAE have been thoroughly characterized [1,2]. 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].…”