CD4 T-cell epitopes of human alpha B-crystallin.
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.
Chou
Yuan K
YK
Department of Neurology, Oregon Health and Science University, Portland, Oregon 97201, USA. chouy@ohsu.edu
Burrows
Gregory G
GG
LaTocha
Dorian
D
Wang
Chunhe
C
Subramanian
Sandhya
S
Bourdette
Dennis N
DN
Vandenbark
Arthur A
AA
D000595:Amino Acid Sequence; D001665:Binding Sites / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020539:Sequence Analysis, Protein / Q000379:methods; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D018984:Epitopes, T-Lymphocyte; D038203:alpha-Crystallin B Chain