Modulation of cytokine patterns of human autoreactive T cell clones by a single amino acid substitution of their peptide ligand

Immunity. 1995 Apr;2(4):373-80. doi: 10.1016/1074-7613(95)90145-0.


We demonstrate that cognate peptide ligands altered at T cell receptor (TCR) contact residues and bound to class II major histocompatability complex can change the cytokine pattern of mature T cell clones. Myelin basic protein peptide 85-99-reactive Th0 T cell clones were stimulated with altered peptide ligands, which acted both as TCR antagonist and induced new mRNA synthesis and protein secretion of TGF-beta 1, while no longer inducing mRNA synthesis or protein secretion of IL-2, IL-4, IL-10, and IFN gamma. The modified peptides failed to induce a detectable calcium flux, p56lck activation, or thymidine incorporation, yet triggered nearly equal amounts of IL-4 secretion in the presence of ionomycin. Antigen-induced modulation of T cell cytokine secretion may be important in regulating the immune response.

Publication types

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

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cells, Cultured
  • Clone Cells
  • Cytokines / biosynthesis*
  • Cytokines / metabolism
  • DNA Primers
  • HLA Antigens / immunology
  • HLA Antigens / metabolism*
  • Humans
  • Molecular Sequence Data
  • Myelin Basic Protein / chemistry
  • Myelin Basic Protein / pharmacology*
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Cytokines
  • DNA Primers
  • HLA Antigens
  • Myelin Basic Protein
  • RNA, Messenger