Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99)

Marco Vergelli, Bernhard Hemmer, Ursula Utz, Anne Vogt, Matthias Kalbus, Laura Tranquill, Paul Conlon, Nicholas Ling, Lawrence Steinman, Henry F. McFarland, Roland Martin

Research output: Contribution to journalArticle

Abstract

We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.

Original languageEnglish (US)
Pages (from-to)2624-2634
Number of pages11
JournalEuropean Journal of Immunology
Volume26
Issue number11
DOIs
StatePublished - 1996
Externally publishedYes

Fingerprint

T-Cell Antigen Receptor
Multiple Sclerosis
Clone Cells
Ligands
T-Lymphocytes
Peptides
Th1 Cells
Interleukin-2 Receptors
Alanine
Up-Regulation
Antigens
myelin basic protein 87-99
Therapeutics

Keywords

  • Altered peptide ligands
  • Autoimmunity
  • Human
  • Myelin basic protein
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology

Cite this

Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99). / Vergelli, Marco; Hemmer, Bernhard; Utz, Ursula; Vogt, Anne; Kalbus, Matthias; Tranquill, Laura; Conlon, Paul; Ling, Nicholas; Steinman, Lawrence; McFarland, Henry F.; Martin, Roland.

In: European Journal of Immunology, Vol. 26, No. 11, 1996, p. 2624-2634.

Research output: Contribution to journalArticle

Vergelli, M, Hemmer, B, Utz, U, Vogt, A, Kalbus, M, Tranquill, L, Conlon, P, Ling, N, Steinman, L, McFarland, HF & Martin, R 1996, 'Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99)', European Journal of Immunology, vol. 26, no. 11, pp. 2624-2634. https://doi.org/10.1002/eji.1830261113
Vergelli, Marco ; Hemmer, Bernhard ; Utz, Ursula ; Vogt, Anne ; Kalbus, Matthias ; Tranquill, Laura ; Conlon, Paul ; Ling, Nicholas ; Steinman, Lawrence ; McFarland, Henry F. ; Martin, Roland. / Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99). In: European Journal of Immunology. 1996 ; Vol. 26, No. 11. pp. 2624-2634.
@article{351d0a96d5484c83bcc5b42fbced4397,
title = "Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99)",
abstract = "We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.",
keywords = "Altered peptide ligands, Autoimmunity, Human, Myelin basic protein, T lymphocyte",
author = "Marco Vergelli and Bernhard Hemmer and Ursula Utz and Anne Vogt and Matthias Kalbus and Laura Tranquill and Paul Conlon and Nicholas Ling and Lawrence Steinman and McFarland, {Henry F.} and Roland Martin",
year = "1996",
doi = "10.1002/eji.1830261113",
language = "English (US)",
volume = "26",
pages = "2624--2634",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "11",

}

TY - JOUR

T1 - Differential activation of human autoreactive T cell clones by altered peptide ligands derived from myelin basic protein peptide (87-99)

AU - Vergelli, Marco

AU - Hemmer, Bernhard

AU - Utz, Ursula

AU - Vogt, Anne

AU - Kalbus, Matthias

AU - Tranquill, Laura

AU - Conlon, Paul

AU - Ling, Nicholas

AU - Steinman, Lawrence

AU - McFarland, Henry F.

AU - Martin, Roland

PY - 1996

Y1 - 1996

N2 - We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.

AB - We have examined the functional consequences induced by interaction of DR2a-restricted myelin basic protein (MBP) (87-99)-specific T cell clones (TCC) with altered peptide ligands (APL) derived from MBP peptide (87-99). The immunodominant MBP peptide (87-99) has been implicated as a candidate antigen in multiple sclerosis (MS) by several lines of evidence. In the present study, we have defined the T cell receptor (TCR) contact residues for DR2a-restricted, (87-99)-specific T helper type 1 T cells to design APL suitable to modify the functions of such T cells potentially relevant for the pathogenesis of MS. We show that neutral (L-alanine substitutions) or conservative exchanges of the primary and secondary TCR contact residues lead to various alterations of T cell function, ranging from differences in interleukin-2 receptor up-regulation to anergy induction and TCR antagonism. The potential usefulness of APL as an immunomodulating therapy for DR2+ MS patients is discussed.

KW - Altered peptide ligands

KW - Autoimmunity

KW - Human

KW - Myelin basic protein

KW - T lymphocyte

UR - http://www.scopus.com/inward/record.url?scp=10244247768&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10244247768&partnerID=8YFLogxK

U2 - 10.1002/eji.1830261113

DO - 10.1002/eji.1830261113

M3 - Article

VL - 26

SP - 2624

EP - 2634

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 11

ER -