An HLA-A2-restricted tyrosinase antigen on melanoma cells results from posttranslational modification and suggests a novel pathway for processing of membrane proteins.
T lymphocytes recognize antigens consisting of peptides presented by class I and II major histocompatibility complex (MHC) molecules. The peptides identified so far have been predictable from the amino acid sequences of proteins. We have identified the natural peptide target of a CTL clone that recognizes the tyrosinase gene product on melanoma cells. The peptide results from posttranslational conversion of asparagine to aspartic acid. This change is of central importance for peptide recognition by melanoma-specific T cells, but has no impact on peptide binding to the MHC molecule. This posttranslational modification has not been previously described for any MHC-associated peptide and represents the first demonstration of posttranslational modification of a naturally processed class I-associated peptide. This observation is relevant to the identification and prediction of potential peptide antigens. The most likely mechanism for production of this peptide leads to the suggestion that antigenic peptides can be derived from proteins that are translated into the endoplasmic reticulum.
Skipper
J C
JC
Department of Microbiology, University of Virginia, Charlottesville 22908, USA.
Hendrickson
R C
RC
Gulden
P H
PH
Brichard
V
V
Van Pel
A
A
Chen
Y
Y
Shabanowitz
J
J
Wolfel
T
T
Slingluff
C L
CL
Boon
T
T
Hunt
D F
DF
Engelhard
V H
VH
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology; D001216:Asparagine / Q000378:metabolism; D001224:Aspartic Acid / Q000096:biosynthesis; D002999:Clone Cells; D000939:Epitopes; D015789:HLA-A2 Antigen; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D014442:Monophenol Monooxygenase / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D000939:Epitopes; D015789:HLA-A2 Antigen; D008565:Membrane Proteins; D010446:Peptide Fragments; D001224:Aspartic Acid; D001216:Asparagine; D014442:Monophenol Monooxygenase