An antigenic peptide produced by peptide splicing in the proteasome.
CD8 T lymphocytes recognize peptides of 8 to 10 amino acids presented by class I molecules of the major histocompatibility complex. Here, CD8 T lymphocytes were found to recognize a nonameric peptide on melanoma cells that comprises two noncontiguous segments of melanocytic glycoprotein gp100(PMEL17). The production of this peptide involves the excision of four amino acids and splicing of the fragments. This process was reproduced in vitro by incubating a precursor peptide of 13 amino acids with highly purified proteasomes. Splicing appears to occur by transpeptidation involving an acyl-enzyme intermediate. Our results reveal an unanticipated aspect of the proteasome function of producing antigenic peptides.
Ludwig Institute for Cancer Research and Cellular Genetics Unit, Université de Louvain, B-1200 Brussels, Belgium.
Nathalie
N
Vigneron
Vincent
V
Stroobant
Jacques
J
Chapiro
Annie
A
Ooms
Gérard
G
Degiovanni
Sandra
S
Morel
Pierre
P
van der Bruggen
Thierry
T
Boon
Benoît J
BJ
Van den Eynde
D000818:Animals; D017951:Antigen Presentation; D019556:COS Cells; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D018274:Electroporation; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008545:Melanoma; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011498:Protein Precursors / Q000378:metabolism; D019154:Protein Splicing; D013602:T-Lymphocytes, Cytotoxic / Q000737:chemistry / Q000276:immunology*; D014162:Transfection; D058951:gp100 Melanoma Antigen
D015234:HLA-A Antigens; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; D009363:Neoplasm Proteins; C548637:PMEL protein, human; D010446:Peptide Fragments; D011498:Protein Precursors; D058951:gp100 Melanoma Antigen; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex