Association of MBP peptides with Hsp70 in normal appearing human white matter

Brett T Lund; Yervand Chakryan; Nazely Ashikian; Lilit Mnatsakanyan; Carolyn J Bevan; Rodrigo Aguilera; Tim Gallaher; Michael W Jakowec

doi:10.1016/j.jns.2006.05.066

Association of MBP peptides with Hsp70 in normal appearing human white matter

J Neurol Sci. 2006 Nov 15;249(2):122-34. doi: 10.1016/j.jns.2006.05.066. Epub 2006 Jul 13.

Authors

Brett T Lund¹, Yervand Chakryan, Nazely Ashikian, Lilit Mnatsakanyan, Carolyn J Bevan, Rodrigo Aguilera, Tim Gallaher, Michael W Jakowec

Affiliation

¹ 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

PMID: 16842822
DOI: 10.1016/j.jns.2006.05.066

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Amino Acid Sequence
Autoantigens / chemistry
Autoantigens / immunology*
Autoantigens / isolation & purification
Brain Chemistry*
Cell Line
Epitopes, T-Lymphocyte / chemistry
Epitopes, T-Lymphocyte / immunology*
Epitopes, T-Lymphocyte / isolation & purification
HSP70 Heat-Shock Proteins / chemistry
HSP70 Heat-Shock Proteins / immunology*
HSP70 Heat-Shock Proteins / isolation & purification
Humans
Immunodominant Epitopes / chemistry
Immunodominant Epitopes / immunology*
Immunodominant Epitopes / isolation & purification
Immunoprecipitation
Molecular Sequence Data
Multiple Sclerosis / immunology*
Multiple Sclerosis / metabolism
Multiple Sclerosis / pathology
Myelin Basic Protein
Myelin Sheath / chemistry*
Nerve Tissue Proteins / chemistry
Nerve Tissue Proteins / immunology*
Nerve Tissue Proteins / isolation & purification
Peptide Fragments / chemistry
Peptide Fragments / immunology*
Peptide Fragments / isolation & purification
Protein Interaction Mapping
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
T-Cell Antigen Receptor Specificity*
T-Lymphocytes / immunology
Transcription Factors / chemistry
Transcription Factors / immunology*
Transcription Factors / isolation & purification

Substances

Adjuvants, Immunologic
Autoantigens
Epitopes, T-Lymphocyte
HSP70 Heat-Shock Proteins
Immunodominant Epitopes
MBP protein, human
Myelin Basic Protein
Nerve Tissue Proteins
Peptide Fragments
Transcription Factors