Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The T-cell response to mutated and normal p53 products of BALB/c-derived Meth A sarcoma was analyzed. Meth A p53 is known to have three missense point mutations in codons 132, 168, and 234, and 24 peptides containing wild-type or mutated sequences at the three mutation sites were constructed. Spleen cells from BALB/c or (BALB/c x C57BL/6)F1 mice immunized with p53 peptides were sensitized in vitro with the corresponding peptides. Because Meth A is resistant to cytotoxic T cells, the sensitive P1-HTR cell line, which expresses a low level of p53 lacking the Meth A p53 mutations, was chosen as a target, either pulse-labeled with p53 peptides or transfected with plasmids containing coding sequences from Meth A p53. One peptide, a nonamer containing the codon 234 mutation (234CM), induced CD8+ cytotoxic T cells that lysed 234CM-pulsed P1-HTR cells in an H-2Kd-restricted fashion. P1-HTR cells pulsed with the corresponding wild-type peptide were only weakly lysed by 234CM-reactive cytotoxic T cells. P1-HTR cells pulsed with other wild-type or mutated p53 peptides were not lysed by 234CM-reactive cytotoxic T cells, nor could these peptides, including 234CW (the wild-type counterpart to 234CM), elicit cytotoxic cells. P1-HTR cells transfected with plasmids coding for the 234CM sequence and expressing high p53 levels were weakly lysed by 234CM-reactive cytotoxic T cells. However, lysis of one of the transfectants was significantly increased by pretreatment with interferon gamma. A proliferative response of CD4+ T cells was elicited by immunization with 234CM and 234CW, but not with other p53-related peptides. The specificity of 234CM-induced CD4+ T cells for 234-region peptides was broader than the reactivity of 234CM-reactive cytotoxic T cells. Mice immunized with 234CM in incomplete Freund's adjuvant showed heightened resistance to Meth A challenge.
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PMID:A mouse mutant p53 product recognized by CD4+ and CD8+ T cells. 790 59

In this analysis, we examined whether peptides derived from a wild-type murine proto-oncogene, c-erbB-2, function as tumor rejection Ags. Expression of murine c-erbB-2 examined by means of reverse transcription-PCR was observed in several normal adult tissues, such as intestine, kidney, and testis. We then transduced human and murine c-erbB-2 cDNA into two mutually noncross-reactive fibrosarcoma lines of BALB/c origin, CMS7 and CMS17. In BALB/c mice immunized with CMS17HE (CMS17 transduced with human c-erbB-2 cDNA), the growth of subsequently challenged CMS7HE (CMS7 transduced with human c-erbB-2 cDNA) was significantly suppressed. CTL against human c-erbB-2-expressing cells were generated from BALB/c spleen cells in vivo and in vitro sensitized by CMS17HE. The CTL activity was also directed against murine c-erbB-2-expressing cells, CMS7ME and CMS17ME, and was blocked by anti-CD8 or anti-Kd mAbs. A series of peptides of human or murine c-erbB-2 compatible with the Kd binding motif was synthesized. The CTL were reactive with P1.HTR (H-2d) pulsed with three of these peptides, p63-71 (human c-erbB-2 derived), p63-71(A) (murine c-erbB-2 derived), and p780-788 (common for human and murine c-erbB-2). Spleen cells immunized in vivo and in vitro with syngeneic spleen cells pulsed with these peptides became cytotoxic for CMS17HE and/or CMS17ME, but not CMS17neo (CMS17 transduced with control vector). The growth of CMS7ME was suppressed in mice immunized with the murine c-erbB-2-derived peptide, p63-71(A) or p780-788. There was no apparent pathologic change in mice that rejected CMS7ME after vaccination with these peptides.
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PMID:Peptides derived from a wild-type murine proto-oncogene c-erbB-2/HER2/neu can induce CTL and tumor suppression in syngeneic hosts. 923 30