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Changes in cytokine secretion induced by altered peptide ligands of myelin basic protein peptide 85-99

Authors :
L J Ausubel
J I Krieger
D A Hafler
Source :
The Journal of Immunology. 159:2502-2512
Publication Year :
1997
Publisher :
The American Association of Immunologists, 1997.

Abstract

Myelin basic protein (MBP)-specific T cells were isolated directly from peripheral blood by stimulation either with native MBPp85-99 or altered peptide ligands (APLs) in which substitutions of the lysine were made at position 93, a TCR contact residue. We report here that the APL 93A could alter the cytokine profile of some autoreactive MBPp85-99 reactive T cell clones, switching them from a Th0 phenotype secreting high concentrations of IL-4, IL-5, and IFN-gamma into Th2 cells secreting significantly less IFN-gamma. However, in vitro stimulation with the 93A peptide, in some instances, induced T cells that responded better to the native MBPp85-99 peptide. Functionally, the APL 93A was shown to act as an antagonist for IFN-gamma secretion. Based on TCR sequencing and single cell cloning, this alteration in cytokine profile was determined to be the result of the differential activation of individual T cell clones. We discuss the implications of these data for the strength of signal model of T cell activation.

Subjects

Subjects :
Immunology
Immunology and Allergy

Details

ISSN :
15506606 and 00221767
Volume :
159
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi...........756391b58e5b4f765a96cfa5e25d1e7b
Full Text :
https://doi.org/10.4049/jimmunol.159.5.2502