Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein.

Abstract

Although T cell responses to the quantitatively major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP), are likely to be of importance in the course of multiple sclerosis (MS), cell-mediated autoimmune responses to other myelin antigens, in particular quantitatively minor myelin antigens, such as myelin-associated glycoprotein (MAG) and the central nervous system-specific myelin oligodendrocyte glycoprotein (MOG), could also play a prevalent role in disease initiation or progression. Highly purified myelin antigens were used in this study to assess cell-mediated immune response to MOG in MS patients, in the context of the reactivity to other myelin antigens, MBP, PLP, and MAG. The greatest incidence of proliferative response by MS peripheral blood lymphocytes was to MOG, as 12 of 24 patients tested reacted and, of these

Interferon‐β therapy reduces CD4+ and CD8+ T‐cell reactivity in multiple sclerosis

“…While being only a minor component of CNS myelin, the highly immunogenic protein MOG is not located in compact myelin like MBP but rather is found on the outer surface of the oligodendrocyte membrane, thereby making it more accessible for cellular and humoral autoimmune mechanisms. 15,28,35,36 The fact that in our own experiments MOG was the better protein, compared to MBP, for distinguishing the T-cell response between healthy donors and untreated MS patients (our own unpublished observations) supports the idea that MOG is the more relevant target in the induction and progression of pathology in MS. 35,37 The vast majority of responding CD8 + T cells appeared to be classical memory T cells that were CD45RO + (Fig. 3), which is in line with earlier studies showing specific enrichment and oligoclonal expansion of Healthy donors 2Á3 ± 1Á1 3Á0 ± 0Á8 3Á7 ± 0Á7 1 Á9 ± 0Á5 1Á9 ± 0Á6 P ns ns ns ns * Untreated patients 3Á7 ± 2Á3 2Á9 ± 0Á9 2Á8 ± 0Á6 2 Á8 ± 0Á6 2Á9 ± 0Á7 P ns ns ns ** * IFN-b-treated patients 4Á7 ± 2Á4 2Á3 ± 0Á7 2Á5 ± 0Á9 1 Á4 ± 1Á1 1Á5 ± 1Á1…”

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

“…MS patients appear to display a significantly higher level of T cell reactivity to MOG than control individuals (12,13,18,21). Moreover, anti-MOG Abs are localized in CNS areas where myelin disintegration and lesion formation are taking place (8,17).…”

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 cultures were incubated for 72 h at 37 C in humidified air containing 7.5% CO 2 . [ 3 H]-thymidine (1 lCi/well) was added for the last 16 h; the cultures were harvested and counted as described previously [57]. The proliferative response is expressed as stimulation index (SI): mean cpm of triplicates in the presence of antigen over mean cpm of triplicates in the absence of antigen (SD 10%).…”