A double mutation of MBP83-99 peptide induces IL-4 responses and antagonizes IFN-? responses
MetadataShow full item record
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 mice with MBP83-99 and mutant [A91]MBP83-99, [E91]MBP83-99, [F91]MBP83-99, [Y91]MBP83-99, and [R91, A96]MBP83-99 peptides, induced IFN-?, and only [R91, A96]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 [Y91]MBP83-99 and [R91,A96]MBP83-99. The double mutant [R91, A96]MBP83-99 was able to antagonize IFN-? production in vitro by T cells against the native MBP83-99 peptide. Antibodies generated to [R91, A96]MBP83-99 did not cross-react with whole MBP protein. Molecular modeling between peptide analogs and H2 I-As demonstrated novel interactions. The [R91, A96]MBP83-99 double mutant peptide analog is the most promising for further therapeutic studies. © 2008 Elsevier B.V. All rights reserved.
Showing items related by title, author, creator and subject.
Altered peptide ligands of myelin basic protein (MBP87-99) conjugated to reduced mannan modulate immune responses in miceKatsara, M.; Yuriev, E.; Ramsland, Paul; Tselios, T.; Deraos, G.; Lourbopoulos, A.; Grigoriadis, N.; Matsoukas, J.; Apostolopoulos, V. (2009)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 ...
Katsara, M.; Yuriev, E.; Ramsland, Paul; Deraos, G.; Tselios, T.; Matsoukas, J.; Apostolopoulos, V. (2008)Multiple sclerosis (MS) is an autoimmune demyelinating disease mediated primarily by CD4+ T cells. The design of peptide mutants of disease-associated myelin epitopes to alter immune responses offers a promising avenue ...
Chuang, Victor; Kragh-Hansen, U.; Otagiri, M. (2002)Gene manipulation techniques open up the possibility of making recombinant human serum albumin (rHSA) or mutants with desirable therapeutic properties and for protein fusion products. rHSA can serve as a carrier in synthetic ...