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.
Zhang
J W
JW
Department of Immunology, Dr. L. Willems Instituut, Universitaire campus, Diepenbeek, Belgium.
Chou
C H
CH
Hashim
G
G
Medaer
R
R
Raus
J C
JC
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