A unique tumor antigen produced by a single amino acid substitution.
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.
Monach
P A
PA
Department of Pathology, University of Chicago, Illinois 60637, USA.
Meredith
S C
SC
Siegel
C T
CT
Schreiber
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000912:Antibodies, Neoplasm / Q000276:immunology; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D001483:Base Sequence; D002999:Clone Cells / Q000276:immunology; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006639:Histidine; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D009381:Neoplasms, Radiation-Induced / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D017354:Point Mutation; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D018417:Th1 Cells / Q000276:immunology*; D014466:Ultraviolet Rays
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D003062:Codon; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D007376:Interleukin-2; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D012269:Ribosomal Proteins; C049650:ribosomal protein L9; D006639:Histidine