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

J Immunol. 1997 Sep 1;159(5):2502-12.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoimmune Diseases / blood
  • Autoimmune Diseases / immunology*
  • Cell Differentiation / drug effects
  • Cell Line
  • Clone Cells
  • Gene Rearrangement, T-Lymphocyte
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / immunology*
  • Interferon-gamma / metabolism*
  • Interleukin-4 / metabolism*
  • Interleukin-5 / metabolism*
  • Lymphocyte Activation
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / immunology*
  • Myelin Basic Protein / chemistry
  • Myelin Basic Protein / immunology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology*
  • Peptide Fragments / pharmacology
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Structure-Activity Relationship
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / metabolism*

Substances

  • Immunodominant Epitopes
  • Interleukin-5
  • Myelin Basic Protein
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta
  • myelin basic protein 85-99
  • Interleukin-4
  • Interferon-gamma