PMID: 11342717May 9, 2001Paper

Enzymatically mediated engineering of multivalent MHC class II-peptide chimeras

Protein Engineering
S CasaresT D Brumeanu

Abstract

We previously reported the genetic engineering of the first soluble, bivalent major histocompatibility complex (MHC) class II-peptide ligand for T-cell receptor (TCR). This ligand binds stably and specifically to cognate T-cells and exhibits immunomodulatory effects in vitro and in vivo. The increase in valence of MHC class II-peptide ligands was shown to parallel their avidity for cognate TCRs and potency in stimulating cognate T-cells. We describe a new enzymatic method to increase the valence of MHC-peptide ligands by cross-linking the N-glycan moieties of dimeric MHC II-peptide units through a flexible, bifunctional polyethylene glycol linker. Using this method, we generated covalently stabilized tetravalent and octavalent MHC II-peptide ligands which bound stably and specifically to cognate TCR and preserved their structural integrity in blood and lymphoid organs for 72 h. Depending on the TCR/CD4 occupancy and degree of TCR/CD4 co-clustering, the multivalent MHC II-peptide ligands polarized efficiently the antigen-specific CD4(+) T-cells toward type 2 cell differentiation or induced T-cell anergy and apoptosis. The enzymatically mediated engineering of multivalent MHC-peptide ligands for cognate TCRs may provide rational ...Continue Reading

References

Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·K MatsuiM M Davis
May 23, 1998·Annual Review of Immunology·M M DavisY Chien
Mar 7, 2002·International Reviews of Immunology·T D BrumeanuS Casares

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Citations

Mar 30, 2004·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Roberto Mallone, Gerald T Nepom
Aug 17, 2002·Current Opinion in Immunology·Emma L Masteller, Jeffrey A Bluestone
Nov 11, 2005·American Journal of Therapeutics·Roberto Mallone, Gerald T Nepom
May 15, 2015·International Reviews of Immunology·Evan L SauerJudith M Greer
Mar 14, 2002·International Reviews of Immunology·S CasaresT D Brumeanu
Jun 8, 2011·Clinical & Developmental Immunology·Slobodan CulinaRoberto Mallone
Feb 28, 2002·Nature Immunology·Sofia CasaresTeodor-Doru Brumeanu
Aug 21, 2007·European Journal of Immunology·Dennis KirchhoffAlexander Scheffold

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