Abstract
Mice immunized against a cancer recognize antigens unique to that cancer, but the molecular structures of such antigens are unknown. We isolated CD4+ T cell clones recognizing an antigen uniquely expressed on the UV-induced tumor 6132A; some clones inhibited the growth of tumors bearing the specific antigen. A T cell hybridoma was used to purify this antigen from nuclear extracts by RP-HPLC and SDS-PAGE using T cell immunoblot assays. A partial amino acid sequence was nearly identical to a sequence in ribosomal protein L9. The cDNA sequence of L9 from 6132A PRO cells differed from the normal sequence at one nucleotide; this mutation encoded histidine instead of leucine at position 47. A synthetic peptide containing this mutation was over 1000-fold more stimulatory of T cells than was the wild-type peptide. These results indicate that this unique tumor antigen is derived from a single amino acid substitution in a cellular protein.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Neoplasm / immunology
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Antigen Presentation
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / genetics*
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Antigens, Neoplasm / immunology
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Antigens, Neoplasm / isolation & purification
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Base Sequence
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Clone Cells / immunology
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Codon / genetics
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DNA Mutational Analysis
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DNA, Complementary / genetics
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DNA, Neoplasm / genetics
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Female
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Histidine
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Hybridomas / immunology
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Immunization
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Interleukin-2 / metabolism
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Lymphocyte Activation
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Molecular Sequence Data
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology
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Neoplasm Proteins / isolation & purification
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Neoplasms, Radiation-Induced / genetics
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Neoplasms, Radiation-Induced / immunology*
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Peptide Fragments / immunology
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Point Mutation*
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Ribosomal Proteins / chemistry
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Ribosomal Proteins / genetics*
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Ribosomal Proteins / immunology
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Sequence Alignment
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Sequence Homology, Amino Acid
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Th1 Cells / immunology*
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Ultraviolet Rays
Substances
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Antibodies, Monoclonal
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Antibodies, Neoplasm
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Antigens, Neoplasm
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Codon
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DNA, Complementary
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DNA, Neoplasm
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Interleukin-2
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Neoplasm Proteins
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Peptide Fragments
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Ribosomal Proteins
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ribosomal protein L9
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Histidine
Associated data
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GENBANK/U17331
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GENBANK/U17332