The immunoprotective MHC II epitope of a chemically induced tumor harbors a unique mutation in a ribosomal protein.
CD4(+) T lymphocyte clones, generated from mice immunized with the methylcholanthrene-induced fibrosarcoma Meth A (H-2(d)), are restricted by I-E(d) and recognize a unique antigen on Meth A. The antigen has been purified and characterized as the ribosomal protein L11. The antigenic epitope is contained within the sequence EYELRKHNFSDTG and is generated by substitution of Asn by His (italic) caused by a single point mutation. The tumor contains the wild-type and the mutated alleles. Immunization of BALB/cJ mice with the mutated epitope but not with the wild-type epitope protects mice against a subsequent challenge with the Meth A sarcoma. Adoptive transfer of CD4(+) clones into BALB/c mice renders the mice specifically resistant to Meth A sarcoma. The mutated L11 epitope is thus shown to be an immunoprotective epitope in vivo by several criteria.
Center for Immunotherapy of Cancer and Infectious Diseases, University of Connecticut School of Medicine, Farmington, CT 06030-1601, USA.
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Srivastava
D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005354:Fibrosarcoma / Q000235:genetics / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D012269:Ribosomal Proteins / Q000235:genetics / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000951:Antigens, Neoplasm; D000939:Epitopes; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; D012269:Ribosomal Proteins; C027624:ribosomal protein L11; C029237:tumor-associated transplantation antigen