Journal article
Presentation of a T Cell Receptor Antagonist Peptide by Immunoglobulins Ablates Activation of T Cells by a Synthetic Peptide or Proteins Requiring Endocytic Processing
The Journal of experimental medicine, Vol.185(6), pp.1043-1054
03/17/1997
DOI: 10.1084/jem.185.6.1043
PMCID: PMC2196232
PMID: 9091578
Abstract
T cell receptor (TCR) antagonism is being considered for inactivation of aggressive T cells and reversal of T cell–mediated autoimmune diseases. TCR antagonist peptides silence aggressive T cells and reverse experimental allergic encephalomyelitis induced with free peptides. However, it is not clear whether free antagonist peptides could reverse natural disease where the antigen is presumably available for endocytic processing and peptides gain access to newly synthesized class II MHC molecules. Using an efficient endocytic presentation system, we demonstrate that a proteolipid protein (PLP) TCR antagonist peptide (PLP-LR) presented on an Ig molecule (IgPLP-LR) abrogates the activation of T cells stimulated with free encephalitogenic PLP peptide (PLP1), native PLP, or an Ig containing PLP1 peptide (Ig-PLP1). Free PLP-LR abolishes T cell activation when the stimulator is free PLP1 peptide, but has no measurable effect when the stimulator is the native PLP or Ig-PLP1. In vivo, Ig-PLP1 induces a T cell response to PLP1 peptide. However, when coadministered with Ig-PLP-LR, the response to PLP1 peptide is markedly reduced whereas the response to PLP-LR is normal. Free PLP-LR coadministered with Ig-PLP1 has no effect on the T cell response to PLP1. These findings indicate that endocytic presentation of an antagonist peptide by Ig outcompete both external and endocytic agonist peptides whereas free antagonist hinders external but not endocytic agonist peptide. Direct contact with antagonist ligand and/or trans-regulation by PLP-LR–specific T cells may be the operative mechanism for Ig-PLP-LR–mediated downregulation of PLP1-specific T cells in vivo. Efficient endocytic presentation of antagonist peptides, which is the fundamental event for either mechanism, may be critical for reversal of spontaneous T cell–mediated autoimmune diseases where incessant endocytic antigen processing could be responsible for T cell aggressivity.
Details
- Title: Subtitle
- Presentation of a T Cell Receptor Antagonist Peptide by Immunoglobulins Ablates Activation of T Cells by a Synthetic Peptide or Proteins Requiring Endocytic Processing
- Creators
- Kevin L Legge - From the Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996; and The Developmental and Genetic Center, University of Tennessee Medical Center, Knoxville, Tennessee 37920Booki Min - From the Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996; and The Developmental and Genetic Center, University of Tennessee Medical Center, Knoxville, Tennessee 37920Nicholas T Potter - From the Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996; and The Developmental and Genetic Center, University of Tennessee Medical Center, Knoxville, Tennessee 37920Habib Zaghouani - From the Department of Microbiology, University of Tennessee, Knoxville, Tennessee 37996; and The Developmental and Genetic Center, University of Tennessee Medical Center, Knoxville, Tennessee 37920
- Resource Type
- Journal article
- Publication Details
- The Journal of experimental medicine, Vol.185(6), pp.1043-1054
- DOI
- 10.1084/jem.185.6.1043
- PMID
- 9091578
- PMCID
- PMC2196232
- ISSN
- 0022-1007
- eISSN
- 1540-9538
- Language
- English
- Date published
- 03/17/1997
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984047995002771
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