Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice

Maria Katsara, Elizabeth Yuriev, Paul A Ramsland, Theodore Tselios, George Deraos, Athanasios Lourbopoulos, Nikolaos Grigoriadis, John Matsoukas, Vasso Apostolopoulos

Research output: Contribution to journalArticleResearchpeer-review

27 Citations (Scopus)

Abstract

P>Mutations of peptides to generate altered peptide ligands, capable of switching immune responses from T helper 1 (Th1) to T helper 2 (Th2), are promising candidates for the immunotherapy of autoimmune diseases such as multiple sclerosis (MS). We synthesized two mutant peptides from myelin basic protein 87-99 (MBP87-99), an immunodominant peptide epitope identified in MS. Mutations of residues K91 and P96, known to be critical T-cell receptor (TCR) contact sites, resulted in the mutant peptides [R91, A96]MBP87-99 and [A91, A96]MBP87-99. Immunization of mice with these altered peptide ligands emulsified in complete Freund s adjuvant induced both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) responses compared with only IFN-gamma responses induced to the native MBP87-99 peptide. It was of interest that [R91, A96]MBP87-99 conjugated to reduced mannan induced 70 less IFN-gamma compared with the native MBP87-99 peptide. However, [A91, A96]MBP87-99 conjugated to reduced mannan did not induce IFN-gamma-secreting T cells, but elicited very high levels of interleukin-4 (IL-4). Furthermore, antibodies generated to [A91, A96]MBP87-99 peptide conjugated to reduced mannan did not cross-react with the native MBP87-99 peptide. By molecular modelling of the mutant peptides in complex with major histocompatibility complex (MHC) class II, I-As, novel interactions were noted. It is clear that the double-mutant peptide analogue [A91, A96]MBP87-99 conjugated to reduced mannan is able to divert immune responses from Th1 to Th2 and is a promising mutant peptide analogue for use in studies investigating potential treatments for MS.
Original languageEnglish
Pages (from-to)521 - 533
Number of pages13
JournalImmunology
Volume128
Issue number4
Publication statusPublished - 2009

Cite this

Katsara, M., Yuriev, E., Ramsland, P. A., Tselios, T., Deraos, G., Lourbopoulos, A., ... Apostolopoulos, V. (2009). Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice. Immunology, 128(4), 521 - 533.
Katsara, Maria ; Yuriev, Elizabeth ; Ramsland, Paul A ; Tselios, Theodore ; Deraos, George ; Lourbopoulos, Athanasios ; Grigoriadis, Nikolaos ; Matsoukas, John ; Apostolopoulos, Vasso. / Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice. In: Immunology. 2009 ; Vol. 128, No. 4. pp. 521 - 533.
@article{f776ce4285e3482c9b27a532a80cf52b,
title = "Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice",
abstract = "P>Mutations of peptides to generate altered peptide ligands, capable of switching immune responses from T helper 1 (Th1) to T helper 2 (Th2), are promising candidates for the immunotherapy of autoimmune diseases such as multiple sclerosis (MS). We synthesized two mutant peptides from myelin basic protein 87-99 (MBP87-99), an immunodominant peptide epitope identified in MS. Mutations of residues K91 and P96, known to be critical T-cell receptor (TCR) contact sites, resulted in the mutant peptides [R91, A96]MBP87-99 and [A91, A96]MBP87-99. Immunization of mice with these altered peptide ligands emulsified in complete Freund s adjuvant induced both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) responses compared with only IFN-gamma responses induced to the native MBP87-99 peptide. It was of interest that [R91, A96]MBP87-99 conjugated to reduced mannan induced 70 less IFN-gamma compared with the native MBP87-99 peptide. However, [A91, A96]MBP87-99 conjugated to reduced mannan did not induce IFN-gamma-secreting T cells, but elicited very high levels of interleukin-4 (IL-4). Furthermore, antibodies generated to [A91, A96]MBP87-99 peptide conjugated to reduced mannan did not cross-react with the native MBP87-99 peptide. By molecular modelling of the mutant peptides in complex with major histocompatibility complex (MHC) class II, I-As, novel interactions were noted. It is clear that the double-mutant peptide analogue [A91, A96]MBP87-99 conjugated to reduced mannan is able to divert immune responses from Th1 to Th2 and is a promising mutant peptide analogue for use in studies investigating potential treatments for MS.",
author = "Maria Katsara and Elizabeth Yuriev and Ramsland, {Paul A} and Theodore Tselios and George Deraos and Athanasios Lourbopoulos and Nikolaos Grigoriadis and John Matsoukas and Vasso Apostolopoulos",
year = "2009",
language = "English",
volume = "128",
pages = "521 -- 533",
journal = "Immunology",
issn = "0019-2805",
publisher = "Wiley-Blackwell",
number = "4",

}

Katsara, M, Yuriev, E, Ramsland, PA, Tselios, T, Deraos, G, Lourbopoulos, A, Grigoriadis, N, Matsoukas, J & Apostolopoulos, V 2009, 'Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice', Immunology, vol. 128, no. 4, pp. 521 - 533.

Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice. / Katsara, Maria; Yuriev, Elizabeth; Ramsland, Paul A; Tselios, Theodore; Deraos, George; Lourbopoulos, Athanasios; Grigoriadis, Nikolaos; Matsoukas, John; Apostolopoulos, Vasso.

In: Immunology, Vol. 128, No. 4, 2009, p. 521 - 533.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in mice

AU - Katsara, Maria

AU - Yuriev, Elizabeth

AU - Ramsland, Paul A

AU - Tselios, Theodore

AU - Deraos, George

AU - Lourbopoulos, Athanasios

AU - Grigoriadis, Nikolaos

AU - Matsoukas, John

AU - Apostolopoulos, Vasso

PY - 2009

Y1 - 2009

N2 - P>Mutations of peptides to generate altered peptide ligands, capable of switching immune responses from T helper 1 (Th1) to T helper 2 (Th2), are promising candidates for the immunotherapy of autoimmune diseases such as multiple sclerosis (MS). We synthesized two mutant peptides from myelin basic protein 87-99 (MBP87-99), an immunodominant peptide epitope identified in MS. Mutations of residues K91 and P96, known to be critical T-cell receptor (TCR) contact sites, resulted in the mutant peptides [R91, A96]MBP87-99 and [A91, A96]MBP87-99. Immunization of mice with these altered peptide ligands emulsified in complete Freund s adjuvant induced both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) responses compared with only IFN-gamma responses induced to the native MBP87-99 peptide. It was of interest that [R91, A96]MBP87-99 conjugated to reduced mannan induced 70 less IFN-gamma compared with the native MBP87-99 peptide. However, [A91, A96]MBP87-99 conjugated to reduced mannan did not induce IFN-gamma-secreting T cells, but elicited very high levels of interleukin-4 (IL-4). Furthermore, antibodies generated to [A91, A96]MBP87-99 peptide conjugated to reduced mannan did not cross-react with the native MBP87-99 peptide. By molecular modelling of the mutant peptides in complex with major histocompatibility complex (MHC) class II, I-As, novel interactions were noted. It is clear that the double-mutant peptide analogue [A91, A96]MBP87-99 conjugated to reduced mannan is able to divert immune responses from Th1 to Th2 and is a promising mutant peptide analogue for use in studies investigating potential treatments for MS.

AB - P>Mutations of peptides to generate altered peptide ligands, capable of switching immune responses from T helper 1 (Th1) to T helper 2 (Th2), are promising candidates for the immunotherapy of autoimmune diseases such as multiple sclerosis (MS). We synthesized two mutant peptides from myelin basic protein 87-99 (MBP87-99), an immunodominant peptide epitope identified in MS. Mutations of residues K91 and P96, known to be critical T-cell receptor (TCR) contact sites, resulted in the mutant peptides [R91, A96]MBP87-99 and [A91, A96]MBP87-99. Immunization of mice with these altered peptide ligands emulsified in complete Freund s adjuvant induced both interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) responses compared with only IFN-gamma responses induced to the native MBP87-99 peptide. It was of interest that [R91, A96]MBP87-99 conjugated to reduced mannan induced 70 less IFN-gamma compared with the native MBP87-99 peptide. However, [A91, A96]MBP87-99 conjugated to reduced mannan did not induce IFN-gamma-secreting T cells, but elicited very high levels of interleukin-4 (IL-4). Furthermore, antibodies generated to [A91, A96]MBP87-99 peptide conjugated to reduced mannan did not cross-react with the native MBP87-99 peptide. By molecular modelling of the mutant peptides in complex with major histocompatibility complex (MHC) class II, I-As, novel interactions were noted. It is clear that the double-mutant peptide analogue [A91, A96]MBP87-99 conjugated to reduced mannan is able to divert immune responses from Th1 to Th2 and is a promising mutant peptide analogue for use in studies investigating potential treatments for MS.

UR - http://www3.interscience.wiley.com.ezproxy.lib.monash.edu.au/journal/122454354/abstract?CRETRY=1&SRETRY=0

M3 - Article

VL - 128

SP - 521

EP - 533

JO - Immunology

JF - Immunology

SN - 0019-2805

IS - 4

ER -