International Immunology, Vol. 15, No. 2, pp. 241-249,
February 2003
© 2003 Japanese Society for Immunology
Heat shock protein 70 associations with myelin basic protein and proteolipid protein in multiple sclerosis brains
Departments of 1 Neurology, and 2 Medical and Molecular Biophysics, Medical University of Lodz, 22, Kopcinskiego Street, 90-153 Lodz, Poland 3 Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, NY 10461, USA
Correspondence to: K. W. Selmaj; E-mail: kselmaj{at}afazja.am.lodz.pl
Transmitting editor: L. Steinman
Heat shock proteins (hsp) are known to facilitate the generation of specific immune responses by chaperoning proteins and peptides involved in T cell activation. Hsp have been shown to be strikingly elevated in multiple sclerosis (MS) lesions. The unique chaperonin properties of hsp70 have allowed identification of immunogenic proteins bound to it by the ex vivo demonstration of hsp associations with proteins implicated in the immune response. We have investigated the association of hsp70 with myelin basic protein (MBP), myelin proteolipid protein (PLP) and myelin oligodendrocyte protein (MOG) in MS and control brain tissue. In co-immunoprecipitation experiments, in all samples of MS brains examined (n = 3), but not control brain tissue (n = 3), direct association of MBP with hsp70, but not with hsp90, was found. In some MS brain samples, association between PLP and hsp70 was also seen. In similar co-immunoprecipitation experiments on brain tissue obtained from mice with experimental autoimmune encephalomyelitis (n = 5) induced by immunization with PLP peptide, specific association of hsp70 with PLP and MBP was found. Using surface plasmon resonance we demonstrated specific binding of hsp70 with MBP in vitro. Analysis of the amounts of MBP bound to hsp70 yielded a molecular ratio of MBP binding to hsp70 at 6.5:1. MBP complexed with hsp70 was taken up at significantly higher rates by antigen-presenting cells than MBP alone and enhanced MBP-specific immune responses. These results indicate that hsp70 specifically associates with MBP in MS brain tissue. This association might be relevant to the enhanced immune recognition of MBP in MS.
Keywords: brain, heat shock protein, multiple sclerosis, myelin
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