Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar Vα and Vβ chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different

F. R. Burns, X. Li, N. Shen, Halina Offner, Y. K. Chou, Arthur Vandenbark, E. Heber-Katz

Research output: Contribution to journalArticle

320 Citations (Scopus)

Abstract

Prospects for specific immune intervention in T cell-mediated autoimmune disease via anti-idiotypic regulation depend on the degree of diversity of the responder cell antigen receptor repertoire. A highly heterogenous response against self epitopes offers little chance for such regulation. We report here that the Lewis rat autoimmune disease experimental allergic encephalomyelitis, generally considered to be a model of human multiple sclerosis, is caused by T cells that use a limited set of TCR V genes. We have cloned the rat TCR α and β chain cDNAs from the Lewis rat x mouse T cell hybridoma 510, which retains the rat specificity for the encephalitogenic determinant of myelin basic protein (MBP). Using Northern blot analysis of T cell RNA with the cloned V region probes, we have found a specific, and near perfect, correlation between expression of TCR message hybridizing to the Vα510 and VB510 probes and specificity for the encephalitogenic determinant of MBP in both T cell hybridomas and encephalitogenic T cell clones. This restricted V gene usage provides a basis for observed idiotypic regulation of auto-reactive T cells, and possible therapy for autoimmune disease. A curious and unexplained observation is that the Lewis rat Vα/Vβ combination that dominates the encephalitogenic response to the 68-88 peptide of MBP is precisely the same Vα/Vβ combination used by the B10.PL mouse response to the encephalitogenic response to the 1-9 peptide of MBP.

Original languageEnglish (US)
Pages (from-to)27-39
Number of pages13
JournalJournal of Experimental Medicine
Volume169
Issue number1
StatePublished - 1989
Externally publishedYes

Fingerprint

Myelin Basic Protein
T-Cell Antigen Receptor
Major Histocompatibility Complex
T-Lymphocytes
Genes
Autoimmune Diseases
Hybridomas
Antigen Receptors
Autoimmune Experimental Encephalomyelitis
Cell- and Tissue-Based Therapy
Northern Blotting
Multiple Sclerosis
Epitopes
Complementary DNA
Clone Cells
Observation
RNA
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

@article{ab0c7e9f677d45578d9dc0c4f3fd0ffe,
title = "Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar Vα and Vβ chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different",
abstract = "Prospects for specific immune intervention in T cell-mediated autoimmune disease via anti-idiotypic regulation depend on the degree of diversity of the responder cell antigen receptor repertoire. A highly heterogenous response against self epitopes offers little chance for such regulation. We report here that the Lewis rat autoimmune disease experimental allergic encephalomyelitis, generally considered to be a model of human multiple sclerosis, is caused by T cells that use a limited set of TCR V genes. We have cloned the rat TCR α and β chain cDNAs from the Lewis rat x mouse T cell hybridoma 510, which retains the rat specificity for the encephalitogenic determinant of myelin basic protein (MBP). Using Northern blot analysis of T cell RNA with the cloned V region probes, we have found a specific, and near perfect, correlation between expression of TCR message hybridizing to the Vα510 and VB510 probes and specificity for the encephalitogenic determinant of MBP in both T cell hybridomas and encephalitogenic T cell clones. This restricted V gene usage provides a basis for observed idiotypic regulation of auto-reactive T cells, and possible therapy for autoimmune disease. A curious and unexplained observation is that the Lewis rat Vα/Vβ combination that dominates the encephalitogenic response to the 68-88 peptide of MBP is precisely the same Vα/Vβ combination used by the B10.PL mouse response to the encephalitogenic response to the 1-9 peptide of MBP.",
author = "Burns, {F. R.} and X. Li and N. Shen and Halina Offner and Chou, {Y. K.} and Arthur Vandenbark and E. Heber-Katz",
year = "1989",
language = "English (US)",
volume = "169",
pages = "27--39",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "1",

}

TY - JOUR

T1 - Both rat and mouse T cell receptors specific for the encephalitogenic determinant of myelin basic protein use similar Vα and Vβ chain genes even though the major histocompatibility complex and encephalitogenic determinants being recognized are different

AU - Burns, F. R.

AU - Li, X.

AU - Shen, N.

AU - Offner, Halina

AU - Chou, Y. K.

AU - Vandenbark, Arthur

AU - Heber-Katz, E.

PY - 1989

Y1 - 1989

N2 - Prospects for specific immune intervention in T cell-mediated autoimmune disease via anti-idiotypic regulation depend on the degree of diversity of the responder cell antigen receptor repertoire. A highly heterogenous response against self epitopes offers little chance for such regulation. We report here that the Lewis rat autoimmune disease experimental allergic encephalomyelitis, generally considered to be a model of human multiple sclerosis, is caused by T cells that use a limited set of TCR V genes. We have cloned the rat TCR α and β chain cDNAs from the Lewis rat x mouse T cell hybridoma 510, which retains the rat specificity for the encephalitogenic determinant of myelin basic protein (MBP). Using Northern blot analysis of T cell RNA with the cloned V region probes, we have found a specific, and near perfect, correlation between expression of TCR message hybridizing to the Vα510 and VB510 probes and specificity for the encephalitogenic determinant of MBP in both T cell hybridomas and encephalitogenic T cell clones. This restricted V gene usage provides a basis for observed idiotypic regulation of auto-reactive T cells, and possible therapy for autoimmune disease. A curious and unexplained observation is that the Lewis rat Vα/Vβ combination that dominates the encephalitogenic response to the 68-88 peptide of MBP is precisely the same Vα/Vβ combination used by the B10.PL mouse response to the encephalitogenic response to the 1-9 peptide of MBP.

AB - Prospects for specific immune intervention in T cell-mediated autoimmune disease via anti-idiotypic regulation depend on the degree of diversity of the responder cell antigen receptor repertoire. A highly heterogenous response against self epitopes offers little chance for such regulation. We report here that the Lewis rat autoimmune disease experimental allergic encephalomyelitis, generally considered to be a model of human multiple sclerosis, is caused by T cells that use a limited set of TCR V genes. We have cloned the rat TCR α and β chain cDNAs from the Lewis rat x mouse T cell hybridoma 510, which retains the rat specificity for the encephalitogenic determinant of myelin basic protein (MBP). Using Northern blot analysis of T cell RNA with the cloned V region probes, we have found a specific, and near perfect, correlation between expression of TCR message hybridizing to the Vα510 and VB510 probes and specificity for the encephalitogenic determinant of MBP in both T cell hybridomas and encephalitogenic T cell clones. This restricted V gene usage provides a basis for observed idiotypic regulation of auto-reactive T cells, and possible therapy for autoimmune disease. A curious and unexplained observation is that the Lewis rat Vα/Vβ combination that dominates the encephalitogenic response to the 68-88 peptide of MBP is precisely the same Vα/Vβ combination used by the B10.PL mouse response to the encephalitogenic response to the 1-9 peptide of MBP.

UR - http://www.scopus.com/inward/record.url?scp=0024530958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0024530958&partnerID=8YFLogxK

M3 - Article

C2 - 2462609

AN - SCOPUS:0024530958

VL - 169

SP - 27

EP - 39

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 1

ER -