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| Content Provider | PubMed Central |
|---|---|
| Author | Noguchi, Y. Chen, Y. T. Old, L. J. |
| Abstract | 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. |
| Starting Page | 3171 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 91 |
| Language | English |
| Publisher Date | 1994-04-12 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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