Time course of T-cell responses to MOG and MBP in patients with clinically isolated syndromes

CD4 + T-cell lines (TCLs) from patients with clinically isolated syndromes (CIS) were selected with purified human myelin basic protein (MBP) and recombinant human myelin oligodendrocyte glycoprotein (rhMOG), at onset of neurological symptoms and when patients developed clinically definite multiple sclerosis (CDMS). The epitope specificity of each TCL was mapped with overlapping synthetic peptides. TCLs were assessed for their ability to secrete IFN-γ, IL-4, and IL-6. Diverse patterns of epitope recognition were observed: (a) recognition of a broad spectrum of MBP peptide epitopes with evidence of shifts over time; (b) an initial T-cell response focused to a restricted segment of the MBP molecule (83–102) that broadened over the course of disease; and (c) persistence of a focused anti-MOG T-cell response. CIS patients who failed to develop CDMS maintained a focused epitope response against two to six MBP epitopes. Most MBP peptide-specific TCLs secreted considerable amounts of IFN-γ and low amounts of IL-4 and IL-6, whereas anti rhMOG Igd peptide-specific TCLs secreted preferentially IL-4 and IL-6. These data raise important issues for the pathogenesis and treatment of multiple sclerosis (MS).