PREDOMINANCE OF THE AUTOIMMUNE-RESPONSE TO MYELIN OLIGODENDROCYTE GLYCOPROTEIN (MOG) IN MULTIPLE-SCLEROSIS - REACTIVITY TO THE EXTRACELLULAR DOMAIN OF MOG IS DIRECTED AGAINST 3 MAIN REGIONS

Our previous analysis of the T cell reactivity to myelin antigens in a group of 24 patients with multiple sclerosis (MS) and 16 control indi viduals revealed that the autoimmune response to myelin oligodendrocyt e glycoprotein (MOG) predominates in MS over that to myelin basic prot ein (MBP), proteolipid protein or myelin-associated glycoprotein, sugg esting a prevalent role for the autoimmune response to MOG in the path ogenesis of MS. Using a recombinant human MOG (rhMOG) preparation corr esponding to the extracellular immunoglobulin-like domain of the MOG m olecule, we have now analyzed another group of 52 MS patients and 49 c ontrol individuals for reactivity of their peripheral blood lymphocyte s (PBL) to rhMOG and to MBP concomitantly. Of the 52 MS patients teste d 24 responded to MOG and 10 out of 49 responded to MBP, whereas only 5 MOG-reactive and 4 MBP-reactive control individuals were detected ou t of the 49 tested. These results are therefore highly confirmatory of the predominant reactivity to MOG in MS. The analysis of the primary proliferative response to II synthetic overlapping peptides (phMOG) sp anning the extracellular domain of human MOG by PBL from 9 MS patients and 15 control individuals (9 healthy controls and 6 patients with ne urological diseases other than MS) further supports a prevalent role f or the autoimmune response to MOG in MS, as only 1 of the 15 controls tested showed reactivity to any of the phMOG, whilst 5 out of the 9 pa tients studied reacted to at least 1 of the phMOG. PBL from 10 MS pati ents, and from 4 controls, were selected in vitro with each of the phM OG. Of the 10 patients studied 7 reacted to at least 1 phMOG upon seco ndary stimulation and the reactivity was mostly directed to epitopes l ocalized within three main regions (amino acids 1-22, 34-56 and 64-96) , as was observed for the primary response of PBL. The predominant res ponse to MOG of PBL from MS patients as demonstrated in two separate s tudies using native MOG and rhMOG as antigens, and the high incidence of reactivity of these PBL compared to the lack of response to phMOG b y control PBL, emphasize the relevance of MOG in MS pathogenesis and s upport a primary role for the autoimmune T cell response to MOG in dis ease development.