To date, any theory of MS pathogenesis must explain the following, undisputed observations: increased MS risk after infectious mononucleosis; elevated immune reactivity to EBV, but not to any other tested pathogen; CD8 T cell predominance in the CNS inflammatory infiltrates; and high therapeutic efficacy of B-cell-depleting anti-CD20 MAbs. Here, CD8A is linked to infectious mononucleosis.