A double mutation of MBP83-99 peptide induces IL-4 responses and antagonizes IFN-gamma responses

Maria Katsara, Elizabeth Yuriev, Paul Allen Ramsland, George Deraos, Theodore Tselios, John Matsoukas, Vasso Apostolopoulos

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Abstract

A number of treatment options are available to multiple sclerosis patients, however this needs to be improved. Herein, we designed and synthesized a number of peptides by mutating principal TCR contact residues based on MBP83-99 peptide epitope. Immunization of SJL/J truce with MBP83-99 and mutant [A(91)]MBP83-99, [E-91]MBP83-99, [F-91]MBP83-99, [Y-91]MBP83-99, and [R-91 A(96)] MBP83-99 peptides, induced IFN-gamma, and only [R-91, A(96)] MBP83-99 mutant peptide was able to induce IL-4 secretion by T cells. T cells against the native MBP83-99 peptide cross-reacted with all peptides except [Y-91]MBP83-99 and [R-91, A(96)]MBP83-99. The double mutant [R-91, A(96)]MBP83-99 was able to antagonize IFN-gamma production in vitro by T cells against the native MBP83-99 peptide. Antibodies generated to [R-91, A(96)]MBP83-99 did not cross-react with whole MBP protein. Molecular modeling between peptide analogs and H2 I-A(s) demonstrated novel interactions. The [R-91, A(96)]MBP83-99 double mutant peptide analog is the most prornising for further therapeutic studies. (c) 2008 Elsevier B.V All rights reserved.
Original languageEnglish
Pages (from-to)77 - 89
Number of pages13
JournalJournal of Neuroimmunology
Volume200
Issue number1-2
Publication statusPublished - 2008

Cite this

Katsara, M., Yuriev, E., Ramsland, P. A., Deraos, G., Tselios, T., Matsoukas, J., & Apostolopoulos, V. (2008). A double mutation of MBP83-99 peptide induces IL-4 responses and antagonizes IFN-gamma responses. Journal of Neuroimmunology, 200(1-2), 77 - 89.
Katsara, Maria ; Yuriev, Elizabeth ; Ramsland, Paul Allen ; Deraos, George ; Tselios, Theodore ; Matsoukas, John ; Apostolopoulos, Vasso. / A double mutation of MBP83-99 peptide induces IL-4 responses and antagonizes IFN-gamma responses. In: Journal of Neuroimmunology. 2008 ; Vol. 200, No. 1-2. pp. 77 - 89.
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abstract = "A number of treatment options are available to multiple sclerosis patients, however this needs to be improved. Herein, we designed and synthesized a number of peptides by mutating principal TCR contact residues based on MBP83-99 peptide epitope. Immunization of SJL/J truce with MBP83-99 and mutant [A(91)]MBP83-99, [E-91]MBP83-99, [F-91]MBP83-99, [Y-91]MBP83-99, and [R-91 A(96)] MBP83-99 peptides, induced IFN-gamma, and only [R-91, A(96)] MBP83-99 mutant peptide was able to induce IL-4 secretion by T cells. T cells against the native MBP83-99 peptide cross-reacted with all peptides except [Y-91]MBP83-99 and [R-91, A(96)]MBP83-99. The double mutant [R-91, A(96)]MBP83-99 was able to antagonize IFN-gamma production in vitro by T cells against the native MBP83-99 peptide. Antibodies generated to [R-91, A(96)]MBP83-99 did not cross-react with whole MBP protein. Molecular modeling between peptide analogs and H2 I-A(s) demonstrated novel interactions. The [R-91, A(96)]MBP83-99 double mutant peptide analog is the most prornising for further therapeutic studies. (c) 2008 Elsevier B.V All rights reserved.",
author = "Maria Katsara and Elizabeth Yuriev and Ramsland, {Paul Allen} and George Deraos and Theodore Tselios and John Matsoukas and Vasso Apostolopoulos",
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Katsara, M, Yuriev, E, Ramsland, PA, Deraos, G, Tselios, T, Matsoukas, J & Apostolopoulos, V 2008, 'A double mutation of MBP83-99 peptide induces IL-4 responses and antagonizes IFN-gamma responses', Journal of Neuroimmunology, vol. 200, no. 1-2, pp. 77 - 89.

A double mutation of MBP83-99 peptide induces IL-4 responses and antagonizes IFN-gamma responses. / Katsara, Maria; Yuriev, Elizabeth; Ramsland, Paul Allen; Deraos, George; Tselios, Theodore; Matsoukas, John; Apostolopoulos, Vasso.

In: Journal of Neuroimmunology, Vol. 200, No. 1-2, 2008, p. 77 - 89.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A double mutation of MBP83-99 peptide induces IL-4 responses and antagonizes IFN-gamma responses

AU - Katsara, Maria

AU - Yuriev, Elizabeth

AU - Ramsland, Paul Allen

AU - Deraos, George

AU - Tselios, Theodore

AU - Matsoukas, John

AU - Apostolopoulos, Vasso

PY - 2008

Y1 - 2008

N2 - A number of treatment options are available to multiple sclerosis patients, however this needs to be improved. Herein, we designed and synthesized a number of peptides by mutating principal TCR contact residues based on MBP83-99 peptide epitope. Immunization of SJL/J truce with MBP83-99 and mutant [A(91)]MBP83-99, [E-91]MBP83-99, [F-91]MBP83-99, [Y-91]MBP83-99, and [R-91 A(96)] MBP83-99 peptides, induced IFN-gamma, and only [R-91, A(96)] MBP83-99 mutant peptide was able to induce IL-4 secretion by T cells. T cells against the native MBP83-99 peptide cross-reacted with all peptides except [Y-91]MBP83-99 and [R-91, A(96)]MBP83-99. The double mutant [R-91, A(96)]MBP83-99 was able to antagonize IFN-gamma production in vitro by T cells against the native MBP83-99 peptide. Antibodies generated to [R-91, A(96)]MBP83-99 did not cross-react with whole MBP protein. Molecular modeling between peptide analogs and H2 I-A(s) demonstrated novel interactions. The [R-91, A(96)]MBP83-99 double mutant peptide analog is the most prornising for further therapeutic studies. (c) 2008 Elsevier B.V All rights reserved.

AB - A number of treatment options are available to multiple sclerosis patients, however this needs to be improved. Herein, we designed and synthesized a number of peptides by mutating principal TCR contact residues based on MBP83-99 peptide epitope. Immunization of SJL/J truce with MBP83-99 and mutant [A(91)]MBP83-99, [E-91]MBP83-99, [F-91]MBP83-99, [Y-91]MBP83-99, and [R-91 A(96)] MBP83-99 peptides, induced IFN-gamma, and only [R-91, A(96)] MBP83-99 mutant peptide was able to induce IL-4 secretion by T cells. T cells against the native MBP83-99 peptide cross-reacted with all peptides except [Y-91]MBP83-99 and [R-91, A(96)]MBP83-99. The double mutant [R-91, A(96)]MBP83-99 was able to antagonize IFN-gamma production in vitro by T cells against the native MBP83-99 peptide. Antibodies generated to [R-91, A(96)]MBP83-99 did not cross-react with whole MBP protein. Molecular modeling between peptide analogs and H2 I-A(s) demonstrated novel interactions. The [R-91, A(96)]MBP83-99 double mutant peptide analog is the most prornising for further therapeutic studies. (c) 2008 Elsevier B.V All rights reserved.

UR - http://www.sciencedirect.com/science/article/pii/S0165572808001951

M3 - Article

VL - 200

SP - 77

EP - 89

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 1-2

ER -