Various mechanisms have been proposed for the initiation of autoimmune responses by autoreactive T-cell clones. One of these, the molecular mimicry hypothesis, postulates that myelin-reactive T-cell clones are activated by foreign antigens. Until recently, sequence homology between self- and foreign antigens was considered necessary for cross-recognition to occur in multiple sclerosis. This article reviews current progress in T-cell receptor immunology that led to modify this view and proposes a role for degenerate T-cell antigen recognition in the induction of autoimmunity.