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 language | English (US) |
|---|---|
| Pages (from-to) | 2624-2634 |
| Number of pages | 11 |
| Journal | European Journal of Immunology |
| Volume | 26 |
| Issue number | 11 |
| DOIs | |
| State | Published - 1996 |
| Externally published | Yes |
Fingerprint
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 journal › Article
}
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
C2 - 8921948
AN - SCOPUS:10244247768
VL - 26
SP - 2624
EP - 2634
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 11
ER -