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By
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From the * Department of Pathology, The University of Chicago, Chicago, Illinois 60637; and the The genetic origins of CD8+ T cell-recognized unique antigens to which mice respond when
immunized with syngeneic tumor cells are unknown. The ultraviolet light-induced murine tumor 8101 expresses an H-2Kb-restricted immunodominant antigen, A, that induces cytolytic CD8+ T cells in vivo A+ 8101 cells are rejected by naive mice while A Department of Chemistry, § Department of Pathology, and Department of Microbiology and the
Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia
22901
8101 tumor cells grow.
To identify the antigen H-2Kb molecules were immunoprecipitated from A+ 8101 cells and
peptides were eluted by acid. The sensitizing peptide was isolated by sequential reverse-phase
HPLC and sequenced using microcapillary HPLC-triple quadruple mass spectrometry. The
peptide, SNFVFAGI, matched the sequence of the DEAD box protein p68 RNA helicase except for a single amino acid substitution, caused by a single nucleotide change. This mutation
was somatic since fibroblasts from the mouse of tumor origin expressed the wild-type sequence. The amino acid substitution created an anchor for binding of the mutant peptide to
H-2Kb. Our results are consistent with mutant p68 being responsible for rejection of the tumor. Several functions of p68, which include nucleolar assembly and inhibition of DNA unwinding, may be mediated through its IQ domain, which was altered by the mutation. This is
the first description of a somatic tumor-specific mutation in the coding region of a nucleic acid
helicase.
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