The Immunodominant Antigen of an Ultraviolet-induced Regressor Tumor Is Generated by a Somatic Point Mutation in the DEAD Box Helicase p68

@article{citeulike:1903975, abstract = {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[-] 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. 10.1084/jem.185.4.695}, author = {Dubey, Purnima and Hendrickson, Ronald C. and Meredith, Stephen C. and Siegel, Christopher T. and Shabanowitz, Jeffrey and Skipper, Jonathan C. and Engelhard, Victor H. and Hunt, Donald F. and Schreiber, Hans }, citeulike-article-id = {1903975}, doi = {10.1084/jem.185.4.695}, journal = {J. Exp. Med.}, keywords = {tumor-rejection}, month = {February}, number = {4}, pages = {695--706}, posted-at = {2007-11-12 20:25:37}, priority = {2}, title = {The Immunodominant Antigen of an Ultraviolet-induced Regressor Tumor Is Generated by a Somatic Point Mutation in the DEAD Box Helicase p68}, url = {http://dx.doi.org/10.1084/jem.185.4.695}, volume = {185}, year = {1997} }

TY - JOUR ID - citeulike:1903975 L3 - citeulike-article-id:1903975 TI - The Immunodominant Antigen of an Ultraviolet-induced Regressor Tumor Is Generated by a Somatic Point Mutation in the DEAD Box Helicase p68 JF - J. Exp. Med. VL - 185 IS - 4 SP - 695 EP - 706 N2 - 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[-] 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. 10.1084/jem.185.4.695 KW - tumor-rejection AU - Dubey, Purnima AU - Hendrickson, Ronald AU - Meredith, Stephen AU - Siegel, Christopher AU - Shabanowitz, Jeffrey AU - Skipper, Jonathan AU - Engelhard, Victor AU - Hunt, Donald AU - Schreiber, Hans PY - 1997/02/17/ UR - http://dx.doi.org/10.1084/jem.185.4.695 ER -