Jm. Vannoort et al., THE SMALL HEAT-SHOCK PROTEIN ALPHA-B-CRYSTALLIN AS CANDIDATE AUTOANTIGEN IN MULTIPLE-SCLEROSIS, Nature, 375(6534), 1995, pp. 798-801
THE identification of key antigens in human autoimmune diseases is a c
rucial step towards the development of specific intervention. The auto
antigen(s) relevant to multiple sclerosis (MS) probably reside in myel
in of the central nervous system, the target of the disease(1). Here w
e examine proliferative responses of human peripheral blood T cells to
the complete collection of myelin proteins fractionated by reversed-p
hase high-performance liquid chromatography. Myelin isolated from MS-a
ffected brain contained a single protein fraction to which T cells fro
m MS patients and from healthy controls showed dominant responses. Thi
s highly immunogenic protein was identified as alpha B-crystallin, a s
mall heat-shock protein. Immunohistochemical examination of MS lesions
revealed the presence of oligodendrocytes and astrocytes with raised
alpha B- crystallin expression, which were not found in unaffected mye
lin. Our findings indicate that alpha B-crystallin serves as immunodom
inant myelin antigen to human T cells when expressed at the elevated l
evels found in active MS lesions.