The present review of the recent literature focuses on antigen-specific immune reactions in multiple sclerosis. New techniques have allowed precise quantitative analysis of the antigen-receptor repertoire of infiltrating T cells in the multiple sclerosis brain. Novel candidate autoantigens, including B-cell autoantigens, have been identified.‘Humanized’animal models allow the functional characterization of human immune molecules in vivo. Finally, several therapeutic trials have recently assessed the clinical benefit of selective immunotherapies.