Identification and synthesis of altered peptides modulating T cell recognition of a synthetic peptide antigen.
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.
Ede
N J
NJ
Department of Microbiology, University of Melbourne, Parkville, Australia.
Chen
W
W
McCluskey
J
J
Jackson
D C
DC
Purcell
A W
AW
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives; D002460:Cell Line; D006183:H-2 Antigens / Q000276:immunology; D007202:Indicators and Reagents; D051379:Mice; D009570:Nitriles; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D007202:Indicators and Reagents; D009570:Nitriles; D009842:Oligopeptides; D001224:Aspartic Acid; C075871:aspartimide