A myelin basic protein peptide is recognized by cytotoxic t cells in the context of four HLA-DR types associated with multiple sclerosis

Roland Martin, Mark D. Howell, Dolores Jaraquemada, Marjorie Flerlage, John Richert, Steven Brostoff, Eric O. Long, Dale E. McFarlin, Henry F. McFarland

Research output: Contribution to journalArticle

Abstract

We have examined previously the peptide specificity of the T cell response to myelin basic protein (MBP) in patients with multiple sclerosis (MS) and healthy controls, and demonstrated that an epitope spanning amino acids 87-106 was frequently recognized. Because this region is encephalitogenic in some experimental animals, it has been postulated that the response to the epitope may have relevance to M.S. In this study, the fine specificity of this response is studied using four well-characterized, monospecific T cell lines from three MS patients and an identical twin of a patient. Each of the lines recognized a peptide with the same core sequence, amino acids 89-99, although the responses were affected to various degrees by truncations at the COOH-or NH2 terminal ends of the 87-106 epitope. Importantly, the epitope was recognized in conjunction with four different HLA-DR molecules. Also, the T cell receptor β chain usage was heterogeneous, and each line expressed a different VDJ sequence. The four HLA-DR molecules restricting the response to this epitope have been shown to be overrepresentedoverrepresentation in MS populations in various geographic areas, suggesting that the response to this region of the MBP molecule may be relevant to the pathogenesis of M.S. These findings may have important implications in designing therapeutic strategies for the disease.

Original languageEnglish (US)
Pages (from-to)19-24
Number of pages6
JournalJournal of Experimental Medicine
Volume173
Issue number1
StatePublished - 1991
Externally publishedYes

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Myelin Basic Protein
HLA-DR Antigens
Multiple Sclerosis
Epitopes
Peptides
Peptide T
T-Lymphocytes
Monozygotic Twins
T-Cell Antigen Receptor
Amino Acid Sequence
Amino Acids
Cell Line
Population

ASJC Scopus subject areas

  • Immunology

Cite this

Martin, R., Howell, M. D., Jaraquemada, D., Flerlage, M., Richert, J., Brostoff, S., ... McFarland, H. F. (1991). A myelin basic protein peptide is recognized by cytotoxic t cells in the context of four HLA-DR types associated with multiple sclerosis. Journal of Experimental Medicine, 173(1), 19-24.

A myelin basic protein peptide is recognized by cytotoxic t cells in the context of four HLA-DR types associated with multiple sclerosis. / Martin, Roland; Howell, Mark D.; Jaraquemada, Dolores; Flerlage, Marjorie; Richert, John; Brostoff, Steven; Long, Eric O.; McFarlin, Dale E.; McFarland, Henry F.

In: Journal of Experimental Medicine, Vol. 173, No. 1, 1991, p. 19-24.

Research output: Contribution to journalArticle

Martin, R, Howell, MD, Jaraquemada, D, Flerlage, M, Richert, J, Brostoff, S, Long, EO, McFarlin, DE & McFarland, HF 1991, 'A myelin basic protein peptide is recognized by cytotoxic t cells in the context of four HLA-DR types associated with multiple sclerosis', Journal of Experimental Medicine, vol. 173, no. 1, pp. 19-24.
Martin, Roland ; Howell, Mark D. ; Jaraquemada, Dolores ; Flerlage, Marjorie ; Richert, John ; Brostoff, Steven ; Long, Eric O. ; McFarlin, Dale E. ; McFarland, Henry F. / A myelin basic protein peptide is recognized by cytotoxic t cells in the context of four HLA-DR types associated with multiple sclerosis. In: Journal of Experimental Medicine. 1991 ; Vol. 173, No. 1. pp. 19-24.
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