T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats

George Hashim, Arthur Vandenbark, Daniel P. Gold, Terry Diamanduros, Halina Offner

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Abstract

The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the Vβ8.5-Jβ2.3 gene combination, with extensive N region additions to both Dβ1 and Dβ2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different Vβ8 subfamily member (Vβ8.5) than the Vβ8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.

Original languageEnglish (US)
Pages (from-to)515-520
Number of pages6
JournalJournal of Immunology
Volume146
Issue number2
StatePublished - Jan 15 1991

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Immunodominant Epitopes
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Cell Line
T-Lymphocyte Epitopes
Myelin Basic Protein
Proteins
Guinea Pigs
Genes
Peptides
Immunomodulation
Pertussis Toxin
Cyclophosphamide
Haplotypes
Antibody Formation
Epitopes

ASJC Scopus subject areas

  • Immunology

Cite this

@article{1aa67a0a76854829bb58b596cfce03c9,
title = "T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats",
abstract = "The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the Vβ8.5-Jβ2.3 gene combination, with extensive N region additions to both Dβ1 and Dβ2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different Vβ8 subfamily member (Vβ8.5) than the Vβ8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.",
author = "George Hashim and Arthur Vandenbark and Gold, {Daniel P.} and Terry Diamanduros and Halina Offner",
year = "1991",
month = "1",
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language = "English (US)",
volume = "146",
pages = "515--520",
journal = "Journal of Immunology",
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T1 - T cell lines specific for an immunodominant epitope of human basic protein define an encephalitogenic determinant for experimental autoimmune encephalomyelitis-resistant LOU/M rats

AU - Hashim, George

AU - Vandenbark, Arthur

AU - Gold, Daniel P.

AU - Diamanduros, Terry

AU - Offner, Halina

PY - 1991/1/15

Y1 - 1991/1/15

N2 - The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the Vβ8.5-Jβ2.3 gene combination, with extensive N region additions to both Dβ1 and Dβ2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different Vβ8 subfamily member (Vβ8.5) than the Vβ8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.

AB - The LOU/M rat (RT-1w) haplotype, although resistant to an encephalitogenic challenge of guinea pig myelin basic protein (Gp-BP)/CFA and unresponsive to Gp-BP, responded strongly to human (Hu)-BP. Both T cell and antibody responses focused on the 110-129 determinant of Hu-BP, and T cells specific for this epitope transferred clinical and histologic experimental autoimmune encephalomyelitis (EAE) to naive LOU/M rats. Moreover, EAE could be induced actively with Hu-BP and a synthetic Hu-S110-129 peptide in CFA, but only with co-immunomodulation by pertussis toxin or cyclophosphamide. Analysis of TCR V region genes revealed the predominant use of the Vβ8.5-Jβ2.3 gene combination, with extensive N region additions to both Dβ1 and Dβ2. These results define the Hu-BP 110-129 peptide sequence as the major encephalitogenic epitope for the LOU/M strain of rat previously considered resistant to EAE, and support the idea that the encephalitogenic property of BP and other CNS Ag for a given MHC is encompassed within immunodominant T cell epitopes. Furthermore, the TCR sequence data indicate the predominant use of a different Vβ8 subfamily member (Vβ8.5) than the Vβ8.2 gene used preferentially by several other rat strains and the PL/J mouse in the T cell response to BP.

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