Identification and synthesis of altered peptides modulating T cell recognition of a synthetic peptide antigen

Biomed Pept Proteins Nucleic Acids. 1995;1(4):231-4.

Abstract

In studies of T cell responses to synthetic peptides we have observed agonist and antagonist activities associated with contaminants identified within the parent synthesis. The synthesis of two candidate analogues implied by a peptide contaminant formed during the synthesis of La 51-58 (IMIKFNRL) has been carried out. The peptide contaminant was 17-18 Da smaller than the parent peptide consistent with a modified asparagine residue at position 6 and so we synthesised both an aspartimide and a nitrile analogue, representing cyclisation or dehydration of the asparagine residue. The candidate aspartimide and nitrile analogues both bound empty MHC class I molecules to form allo determinants recognised by monoclonal antibodies. These results demonstrate that altered synthetic peptides can bind class I MHC molecules and prompt caution in the use of synthetic peptides as a source of immunising antigen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Cell Line
  • H-2 Antigens / immunology
  • Indicators and Reagents
  • Mice
  • Nitriles
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • H-2 Antigens
  • H-2Kb protein, mouse
  • Indicators and Reagents
  • Nitriles
  • Oligopeptides
  • Aspartic Acid
  • aspartimide