CD4 T-cell epitopes of human alpha B-crystallin.

Abstract

Of potential importance to multiple sclerosis (MS), oligodendroglial alpha B-crystallin is expressed and associated with the myelin sheath at the earliest stage of MS lesion development. We selected T-cell lines specific for human alpha B-crystallin from peripheral blood mononuclear cells (PBMC) of HLA-DR2 homozygous MS patients and found that the alpha B-crystallin-specific T-cells were CD4+ and restricted by DRB1*1501, and expressed Th1 cytokines. The CD4 T-cell epitopes of human alpha B-crystallin were determined by proliferation of alpha B-crystallin-specific T-cell lines to 17 20-mer synthetic overlapping peptides spanning the entire molecule of human alpha B-crystallin. It was found that the HLA-DR2 donor-derived alpha B-crystallin-specific T-cell lines proliferated to alpha B-crystallin peptides 21-40, 41-60, and to a lesser extent, 131-150. These T-cell proliferation responses were associated with intracellular expression of interleukin-2 (IL-2) and secretion of interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha). The amino acid sequences of these peptides were compatible with predicted HLA-DR2-restricted binding motifs. PBMC of an early active MS patient proliferated to the epitope-containing peptides significantly better than did those of later stage MS patients or healthy controls. Taken together, these findings suggest that autoreactive alpha B-crystallin-specific Th1 cells may have the potential to contribute to MS pathogenesis.

• Authors: Yuan K Chou, Gregory G Burrows, Dorian LaTocha, Chunhe Wang, Sandhya Subramanian, Dennis N Bourdette, Arthur A Vandenbark
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 75 Issue 4 Pg. 516-23 (Feb 15 2004) ISSN: 0360-4012 [Print] United States
• PMID: 14743435 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 Wiley-Liss, Inc.

Chemical References

• Epitopes, T-Lymphocyte
• alpha-Crystallin B Chain

Topics

• Amino Acid Sequence
• Binding Sites (immunology)
• CD4-Positive T-Lymphocytes (cytology, immunology, metabolism)
• Cell Division (immunology)
• Cell Line
• Epitopes, T-Lymphocyte (genetics, immunology, metabolism)
• Humans
• Lymphocyte Activation (immunology)
• Molecular Sequence Data
• Multiple Sclerosis (genetics, immunology, metabolism)
• Sequence Analysis, Protein (methods)
• alpha-Crystallin B Chain (genetics, immunology, metabolism)