CD4 T-Cell Epitopes of Human α B-Crystallin

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.