THE identification of key antigens in human autoimmune diseases is a crucial step towards the development of specific intervention. The autoantigen(s) relevant to multiple sclerosis (MS) probably reside in myelin of the central nervous system, the target of the disease¹. Here we examine proliferative responses of human peripheral blood T cells to the complete collection of myelin proteins fractionated by reversed-phase high-performance liquid chro-matography. Myelin isolated from MS-affected brain contained a single protein fraction to which T cells from MS patients and from healthy controls showed dominant responses. This highly immuno-genic protein was identified as αB-crystallin, a small heat-shock protein. Immunohistochemical examination of MS lesions revealed the presence of oligodendrocytes and astrocytes with raised αB-crystallin expression, which were not found in unaffected myelin. Our findings indicate that αB-crystallin serves as immunodominant myelin antigen to human T cells when expressed at the elevated levels found in active MS lesions.