Myelin basic protein–specific T lymphocytes in multiple sclerosis and controls: Precursor frequency, fine specificity, and cytotoxicity

Abstract

A panel of 90 myelin basic protein (MBP)-specific T-cell lines were derived from peripheral blood of eight patients with multiple sclerosis and four normal subjects. The precursor frequency of MBP-reactive T cells in peripheral blood mononuclear cells ranged from 10⁻⁷ to 9 × 10⁻⁷ (mean, 6.7 × 10⁻⁷) in the group of patients with multiple sclerosis and from 0.5 × 10⁻⁷ to 9.8 × 10⁻⁷ (mean, 5.6 × 10⁻⁷) in the control subjects. This difference between the two groups was not statistically significant (p > 0.1). These T-cell lines expressed exclusively CD3+CD4+CD8- phenotypes and were restricted predominantly by HLA-DR molecules. When tested with fragments and synthetic peptides of human MBP, these MBP-specific T-cell lines (45 lines for each group) displayed a limited heterogeneous pattern with a biased recognition to peptide 84-102 and the C-terminal peptide 149-171. The reactivity to the 84-102 region of MBP was associated with the HLA-DR2, DRw15 (DRwl5,2) haplotype, whereas the recognition to peptide 149-171 did not correlate with a particular HLA-DR allele(s). Furthermore, the majority of T-cell lines (>75%) were found to exhibit substantial cytotoxic activity against MBP-coated target cells, but showing no significant difference between these two groups. This MBP-dependent Cytotoxicity was not associated with epitope specificities of the T-cell lines tested.