TY - JOUR
T1 - CD4 T-Cell Epitopes of Human α B-Crystallin
AU - Chou, Yuan K.
AU - Burrows, Gregory G.
AU - LaTocha, Dorian
AU - Wang, Chunhe
AU - Subramanian, Sandhya
AU - Bourdette, Dennis N.
AU - Vandenbark, Arthur A.
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2004/2/15
Y1 - 2004/2/15
N2 - Of potential importance to multiple sclerosis (MS), oligodendroglial α 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 α B-crystallin from peripheral blood mononuclear cells (PBMC) of HLA-DR2 homozygous MS patients and found that the α B-crystallin-specific T-cells were CD4+ and restricted by DRB1*1501, and expressed Th1 cytokines. The CD4 T-cell epitopes of human α B-crystallin were determined by proliferation of α B-crystallin-specific T-cell lines to 17 20-mer synthetic overlapping peptides spanning the entire molecule of human α B-crystallin. It was found that the HLA-DR2 donor-derived α B-crystallin-specific T-cell lines proliferated to α 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-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). 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 α B-crystallin-specific Th1 cells may have the potential to contribute to MS pathogenesis.
AB - Of potential importance to multiple sclerosis (MS), oligodendroglial α 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 α B-crystallin from peripheral blood mononuclear cells (PBMC) of HLA-DR2 homozygous MS patients and found that the α B-crystallin-specific T-cells were CD4+ and restricted by DRB1*1501, and expressed Th1 cytokines. The CD4 T-cell epitopes of human α B-crystallin were determined by proliferation of α B-crystallin-specific T-cell lines to 17 20-mer synthetic overlapping peptides spanning the entire molecule of human α B-crystallin. It was found that the HLA-DR2 donor-derived α B-crystallin-specific T-cell lines proliferated to α 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-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). 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 α B-crystallin-specific Th1 cells may have the potential to contribute to MS pathogenesis.
KW - CD4 T-cells
KW - Human α B-crystallin
KW - Multiple sclerosis
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U2 - 10.1002/jnr.20000
DO - 10.1002/jnr.20000
M3 - Article
C2 - 14743435
AN - SCOPUS:0742270428
SN - 0360-4012
VL - 75
SP - 516
EP - 523
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 4
ER -