Preferential peptide specificity and HLA restriction of myelin basic protein-specific T cell clones derived from MS patients.
A panel of 17 myelin basic protein (MBP)-specific T lymphocyte clones were generated from four multiple sclerosis (MS) patients. All T cell clones expressed CD4 phenotype and 14 clones exhibited substantial cytotoxic activity on MBP-coated target cells. T cell recognition sites of the clones on human MBP were identified by using MBP fragments and synthetic peptides. Despite the fact that at least three epitopes were defined, these T cell clones displayed a striking bias to the C-terminal peptide 149-171 independent of differences in HLA-DR and DQ expression. In addition, the T cell responses of the clones appeared to be restricted by HLA-DR molecules irrespective of peptide specificities. The present study suggests an immunodominant property of the C-terminal peptide for HLA-DR-restricted T cell responses to MBP. However, its association with encephalitogenicity in humans and its potential pathologic importance in MS await further clarification.
Department of Immunology, Dr. L. Willems Instituut, Universitaire campus, Diepenbeek, Belgium.
J W
JW
Zhang
C H
CH
Chou
G
G
Hashim
R
R
Medaer
J C
JC
Raus
D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006681:HLA-D Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments