Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals

Roland Martin, Dolores Jaraquemada, Marjorie Flerlage, John Richert, John Whitaker, Eric O. Long, Dale E. McFarlin, Henry F. McFarland

Research output: Contribution to journalArticle

Abstract

Myelin basic protein (MBP) is a candidate Ag for the autoimmune process believed to be involved in the pathogenesis of multiple sclerosis (MS). To investigate the fine specificity and HLA restriction of human MBP-specific CTL, long term T cell lines (TCL) were established from 22 MS patients and 16 healthy individuals by repeated antigenic restimulation. By using this approach, MBP-specific cytotoxic TCL were generated from 81 % of the lines from MS patients and 69% of those from controls. TCL from both groups expressed the CD3+, CD4+, CD8- phenotype and secreted substantial amounts of IFN-γ. By using large enzymatic and small synthetic peptides of MBP, TCL were primarily specific for the C-terminal part of the molecule and to a lesser extent for the N-terminal portion. Two regions of the molecule, MBP peptide 87-106 and MBP peptide 154-172, were recognized by the majority of the polyspecific lines and by four and three of 14 monospecific TCL, respectively. These highly immunogenic regions are of interest because they include sequences encephalitogenic in other species. The HLA restriction of each line was determined by using antibody blocking as well as various target cells including EBV-transformed B cells, homozygous typing cells, and fibroblasts transfected with cDNA for DR-α and DR-β genes. All TCL were restricted by HLA-DR Ag. Several HLA-DR molecules restricted multiple cathepsin D-derived and synthetic MBP peptides, including the regions of peptides 87-106 and 154-172 which, respectively, were recognized in conjunction with four and three HLA-DR types. Three of these HLA-DR types are overrepresented in MS patients in different geographic regions. Together, these findings suggest that the MBP-specific cytotoxic T cell response, although not sufficient for disease, may be important for the pathogenesis of MS.

Original languageEnglish (US)
Pages (from-to)540-548
Number of pages9
JournalJournal of Immunology
Volume145
Issue number2
StatePublished - Jul 15 1990
Externally publishedYes

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Myelin Basic Protein
Multiple Sclerosis
T-Lymphocytes
Cell Line
HLA-DR Antigens
Peptides
Cathepsin D
Blocking Antibodies
Human Herpesvirus 4
B-Lymphocytes
Complementary DNA
Fibroblasts
Phenotype
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Martin, R., Jaraquemada, D., Flerlage, M., Richert, J., Whitaker, J., Long, E. O., ... McFarland, H. F. (1990). Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. Journal of Immunology, 145(2), 540-548.

Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. / Martin, Roland; Jaraquemada, Dolores; Flerlage, Marjorie; Richert, John; Whitaker, John; Long, Eric O.; McFarlin, Dale E.; McFarland, Henry F.

In: Journal of Immunology, Vol. 145, No. 2, 15.07.1990, p. 540-548.

Research output: Contribution to journalArticle

Martin, R, Jaraquemada, D, Flerlage, M, Richert, J, Whitaker, J, Long, EO, McFarlin, DE & McFarland, HF 1990, 'Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals', Journal of Immunology, vol. 145, no. 2, pp. 540-548.
Martin, Roland ; Jaraquemada, Dolores ; Flerlage, Marjorie ; Richert, John ; Whitaker, John ; Long, Eric O. ; McFarlin, Dale E. ; McFarland, Henry F. / Fine specificity and HLA restriction of myelin basic protein-specific cytotoxic T cell lines from multiple sclerosis patients and healthy individuals. In: Journal of Immunology. 1990 ; Vol. 145, No. 2. pp. 540-548.
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abstract = "Myelin basic protein (MBP) is a candidate Ag for the autoimmune process believed to be involved in the pathogenesis of multiple sclerosis (MS). To investigate the fine specificity and HLA restriction of human MBP-specific CTL, long term T cell lines (TCL) were established from 22 MS patients and 16 healthy individuals by repeated antigenic restimulation. By using this approach, MBP-specific cytotoxic TCL were generated from 81 {\%} of the lines from MS patients and 69{\%} of those from controls. TCL from both groups expressed the CD3+, CD4+, CD8- phenotype and secreted substantial amounts of IFN-γ. By using large enzymatic and small synthetic peptides of MBP, TCL were primarily specific for the C-terminal part of the molecule and to a lesser extent for the N-terminal portion. Two regions of the molecule, MBP peptide 87-106 and MBP peptide 154-172, were recognized by the majority of the polyspecific lines and by four and three of 14 monospecific TCL, respectively. These highly immunogenic regions are of interest because they include sequences encephalitogenic in other species. The HLA restriction of each line was determined by using antibody blocking as well as various target cells including EBV-transformed B cells, homozygous typing cells, and fibroblasts transfected with cDNA for DR-α and DR-β genes. All TCL were restricted by HLA-DR Ag. Several HLA-DR molecules restricted multiple cathepsin D-derived and synthetic MBP peptides, including the regions of peptides 87-106 and 154-172 which, respectively, were recognized in conjunction with four and three HLA-DR types. Three of these HLA-DR types are overrepresented in MS patients in different geographic regions. Together, these findings suggest that the MBP-specific cytotoxic T cell response, although not sufficient for disease, may be important for the pathogenesis of MS.",
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