Cross-reactive T cells recognizing both MBP93-105 and HHV-61-13 peptides represent a significant subset of T cells with some degree of TCR degeneracy. It appears that the recognition of the cross-reactive T cells has a less stringent requirement for the flanking residues of the two peptides. In contrast, these flanking residues are critical for the T cell recognition of mono-specific T cells. The association between HHV-6 and autoreactive immune responses to MBP indicates that cross-reactive T cells, peptides from the V-D-J region of the T cell receptor from autoreactive T cells, and antiviral agents may prevent or treat MS.