A unique tumor antigen produced by a single amino acid substitution

Immunity. 1995 Jan;2(1):45-59. doi: 10.1016/1074-7613(95)90078-0.

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

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neoplasm / immunology
  • Antigen Presentation
  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / isolation & purification
  • Base Sequence
  • Clone Cells / immunology
  • Codon / genetics
  • DNA Mutational Analysis
  • DNA, Complementary / genetics
  • DNA, Neoplasm / genetics
  • Female
  • Histidine
  • Hybridomas / immunology
  • Immunization
  • Interleukin-2 / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / isolation & purification
  • Neoplasms, Radiation-Induced / genetics
  • Neoplasms, Radiation-Induced / immunology*
  • Peptide Fragments / immunology
  • Point Mutation*
  • Ribosomal Proteins / chemistry
  • Ribosomal Proteins / genetics*
  • Ribosomal Proteins / immunology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Th1 Cells / immunology*
  • Ultraviolet Rays

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neoplasm
  • Antigens, Neoplasm
  • Codon
  • DNA, Complementary
  • DNA, Neoplasm
  • Interleukin-2
  • Neoplasm Proteins
  • Peptide Fragments
  • Ribosomal Proteins
  • ribosomal protein L9
  • Histidine

Associated data

  • GENBANK/U17331
  • GENBANK/U17332