TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs

Kevin L Legge; Booki Min; Aimee E Cestra; Christopher D Pack; Habib Zaghouani

doi:10.4049/jimmunol.161.1.106

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TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs

Journal article

Peer reviewed

TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs

Kevin L Legge, Booki Min, Aimee E Cestra, Christopher D Pack and Habib Zaghouani

The Journal of immunology (1950), Vol.161(1), pp.106-111

07/01/1998

DOI: 10.4049/jimmunol.161.1.106

PMID: 9647213

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Abstract

Ig-PLP1 and Ig-PLP-LR are chimeric Igs expressing proteolipid protein (PLP)-derived T cell agonist (PLP1) and antagonist (PLP-LR) peptides, respectively. Both chimeras, like free PLP1 and PLP-LR peptides, induce in vivo-specific T cell responses. However, the responses induced by Ig-PLP1 and Ig-PLP-LR were cross-reactive with both PLP1 and PLP-LR peptides, while those induced by free peptides were not. Surprisingly, despite the cross-reactivity of the responses, when Ig-PLP1 and Ig-PLP-LR were administered together into mice, a dose-dependent down-regulation of both T cell responses and a reduction of IL-2 production to background levels was observed. In contrast, when T cells induced by either Ig chimera were stimulated in vitro with mixtures of free PLP1 and PLP-LR peptides, there was no down-regulation of proliferation or decrease in IL-2 production. These data indicate that Ig-PLP1 and Ig-PLP-LR exert adverse reactions on one another at the level of naive T cells, resulting in an opposite antagonism. However, naive T cells experiencing either chimera develop into cross-reactive cells, acquire resistance to TCR triggering by closely related but different peptides, and support responsiveness.

Recombinant Fusion Proteins - immunology

T-Lymphocyte Subsets - immunology

Myelin Proteolipid Protein - immunology

Peptide Fragments - metabolism

Lymphocyte Activation

Immunoglobulins - genetics

Mice, Inbred Strains

Receptors, Antigen, T-Cell - antagonists & inhibitors

Recombinant Fusion Proteins - metabolism

Immunoglobulins - metabolism

Animals

Antigen Presentation

Myelin Proteolipid Protein - genetics

T-Lymphocyte Subsets - metabolism

Peptide Fragments - immunology

Myelin Proteolipid Protein - metabolism

Receptors, Antigen, T-Cell - agonists

Receptors, Antigen, T-Cell - immunology

Mice

Peptide Fragments - genetics

Details

Title: Subtitle: TCR agonist and antagonist exert in vivo cross-regulation when presented on Igs
Creators: Kevin L Legge - Department of Microbiology, University of Tennessee, Knoxville 37996, USA
Booki Min
Aimee E Cestra
Christopher D Pack
Habib Zaghouani
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.161(1), pp.106-111
DOI: 10.4049/jimmunol.161.1.106
PMID: 9647213
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Language: English
Date published: 07/01/1998
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047620202771

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