Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen Presentation*
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COS Cells
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Cell Line, Tumor
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Cysteine Endopeptidases / metabolism*
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Electroporation
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HLA-A Antigens / immunology
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Humans
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Interferon-gamma / biosynthesis
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Melanoma
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / immunology*
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Membrane Glycoproteins / metabolism
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Models, Chemical
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Multienzyme Complexes / metabolism*
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / immunology*
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Neoplasm Proteins / metabolism
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Peptide Fragments / immunology*
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Peptide Fragments / metabolism
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Proteasome Endopeptidase Complex
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Protein Precursors / metabolism
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Protein Splicing*
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T-Lymphocytes, Cytotoxic / chemistry
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T-Lymphocytes, Cytotoxic / immunology*
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Transfection
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gp100 Melanoma Antigen
Substances
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HLA-A Antigens
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Membrane Glycoproteins
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Multienzyme Complexes
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Neoplasm Proteins
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PMEL protein, human
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Peptide Fragments
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Protein Precursors
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gp100 Melanoma Antigen
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Interferon-gamma
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex