Myelin basic protein-specific T lymphocytes in multiple sclerosis and controls: precursor frequency, fine specificity, and cytotoxicity.
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 x 10(-7) (mean, 6.7 x 10(-7)) in the group of patients with multiple sclerosis and from 0.5 x 10(-7) to 9.8 x 10(-7) (mean, 5.6 x 10(-7)) in the control subjects. This difference between the two groups was not statistically significant (p greater than 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 (DRw15,2) 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 (greater than 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.
Jingwu
Z
Z
Multiple Sclerosis Research Laboratory, Dr L. Willems Instituut, Belgium.
Medaer
R
R
Hashim
G A
GA
Chin
Y
Y
van den Berg-Loonen
E
E
Raus
J C
JC
D000328:Adult; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006680:HLA Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments