The IgG-anti-EBNA1 antibody concentrations are particularly elevated in patients with MS [13, 14, 16, 18, [23] [24] [25] , and systematic studies on the T-helper cell epitopes in the EBNA1 protein revealed that CD4 ? T-cells from healthy EBV carriers matched for MS-associated HLA-DR alleles recognised several epitopes within the central region of the C-terminal domain of this protein but not other EBVencoded proteins [36, 37] . In contrast, those from MS patients recognised many more epitopes spread over the entire domain [36] . Concomitantly, the number of memory T-cells directed against this domain is increased about tenfold in MS and have been shown to be T-helper 1 cell precursors and polarised effector memory cells [36, 37] , containing a subfraction of regulatory T-cells (T reg s) [38, 39] . T reg s were suppressed in MS [40] , and high level of CD8 ? T-cell activation against EBV but not cytomegalovirus was demonstrated early in the course of MS [41] .