The immunodominant antigen of an ultraviolet-induced regressor tumor is generated by a somatic point mutation in the DEAD box helicase p68.
The immunodominant antigen of an ultraviolet-induced regressor tumor is generated by a somatic point mutation in the DEAD box helicase p68.
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DOI：
10.1084/jem.185.4.695
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发表时间：
1997-02-17
期刊：
影响因子：
--
通讯作者：
Schreiber H
中科院分区：
文献类型：
--
作者：
Dubey P;Hendrickson RC;Meredith SC;Siegel CT;Shabanowitz J;Skipper JC;Engelhard VH;Hunt DF;Schreiber H
当用同源肿瘤细胞免疫时，小鼠对CD 8 + T细胞识别的独特抗原的遗传起源是未知的。紫外线诱导的小鼠肿瘤8101表达H-2Kb限制性免疫显性抗原A，其在体内诱导细胞溶解性CD 8 + T细胞A+ 8101细胞被幼稚小鼠排斥，而A− 8101肿瘤细胞生长。为了鉴定抗原，从A+ 8101细胞中免疫沉淀H-2Kb分子，并用酸洗脱肽。通过顺序反相HPLC分离致敏肽，并使用微毛细管HPLC-三重四重质谱法进行测序。肽SNFVFAGI与DEAD盒蛋白p68 RNA解旋酶的序列相匹配，除了由单个核苷酸变化引起的单个氨基酸取代。该突变是体细胞的，因为来自肿瘤来源的小鼠的成纤维细胞表达野生型序列。氨基酸取代产生了突变肽与H-2Kb结合的锚。我们的结果与突变型p68负责肿瘤的排斥反应是一致的。p68的几种功能，包括核仁组装和抑制DNA解旋，可能是通过其IQ结构域介导的，这是由突变改变。这是第一个描述的体细胞肿瘤特异性突变的编码区的核酸解旋酶。
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.
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DOI：
10.1084/jem.179.3.921
发表时间：
1994-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gaugler B;Van den Eynde B;van der Bruggen P;Romero P;Gaforio JJ;De Plaen E;Lethé B;Brasseur F;Boon T
通讯作者：
Boon T
影响因子：
6.4
作者：
CARBONE, G;BORRELLO, MG;PARMIANI, G
通讯作者：
PARMIANI, G
影响因子：
32.4
作者：
BOEL, P;WILDMANN, C;VANDERBRUGGEN, P
通讯作者：
VANDERBRUGGEN, P
DOI：
10.1073/pnas.83.17.6233
发表时间：
1986-09-01
影响因子：
11.1
作者：
HUNT, DF;YATES, JR;HAUER, CR
通讯作者：
HAUER, CR
DOI：
10.1073/pnas.93.18.9730
发表时间：
1996-09-03
影响因子：
11.1
作者：
Huang, AYC;Gulden, PH;Jaffee, EM
通讯作者：
Jaffee, EM