Association of MBP peptides with Hsp70 in normal appearing human white matter.
Multiple Sclerosis is an autoimmune disease directed against myelin proteins. The etiology of MS is poorly defined though, with no definitive causative agent yet identified. It has been hypothesized that MS may be a multifactorial disease resulting in the same end product: the destruction of myelin by the immune system. In this report we describe a potential role for heat shock proteins in the pathogenesis of MS. We isolated Hsp70 from the normal appearing white matter of both MS and normal human brain and found this was actively associated with, among other things, immunodominant MBP peptides. Hsp70-MBP peptide complexes prepared in vitro were shown to be highly immunogenic, with adjuvant-like effects stimulating MBP peptide-specific T cell lines to respond to normally sub-optimal concentrations of peptide. This demonstration of a specific interaction between Hsp70 and different MBP peptides, coupled with the adjuvanticity of this association is suggestive of a possible role for Hsp70 in the immunopathology associated with MS.
Lund
Brett T
BT
Department of Neurology, Keck School of Medicine, University of Southern California, McKibben Annex, Room 246, 1333 San Pablo Street, Los Angeles, California 90033, United States. blund@usc.edu
Chakryan
Yervand
Y
Ashikian
Nazely
N
Mnatsakanyan
Lilit
L
Bevan
Carolyn J
CJ
Aguilera
Rodrigo
R
Gallaher
Tim
T
Jakowec
Michael W
MW
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D001923:Brain Chemistry; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004676:Myelin Basic Protein; D009186:Myelin Sheath / Q000737:chemistry*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification; D025941:Protein Interaction Mapping; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology; D014157:Transcription Factors / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification
D000276:Adjuvants, Immunologic; D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D016056:Immunodominant Epitopes; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D014157:Transcription Factors