| First Author | Morgan DJ | Year | 1998 |
| Journal | J Immunol | Volume | 160 |
| Issue | 2 | Pages | 643-51 |
| PubMed ID | 9551898 | Mgi Jnum | J:45169 |
| Mgi Id | MGI:1194482 | Doi | 10.4049/jimmunol.160.2.643 |
| Citation | Morgan DJ, et al. (1998) Activation of low avidity CTL specific for a self epitope results in tumor rejection but not autoimmunity. J Immunol 160(2):643-51 |
| abstractText | To determine how self-tolerance can alter the ability of the immune system to respond against tumor-associated Ags that are also expressed by normal tissue, we designed experiments in which the same protein was expressed both as a tumor Ag and as a transgene product. Unlike conventional BALB/c mice that rejected renal carcinoma cells transfected with the influenza virus hemagglutinin (Renca-HA), transgenic mice that are tolerant of HA due to its expression as a self-Ag on pancreatic islet beta cells, (Ins-HA mice) supported progressive growth of these tumor cells. However, when Ins-HA mice were immunized with a recombinant strain of vaccinia virus expressing the dominant H-2Kd peptide epitope of HA before receiving Renca-HA cells, they too were able to reject the tumor cells. Rejection of Renca-HA cells by immunized Ins-HA mice was found to be associated with the generation of CTL having much lower avidity for target cells presenting the KdHA epitope than CTL from immunized conventional BALB/c mice. Significantly, we show that self-tolerance to the HA Ag is quantitative rather then absolute, and that vaccination of Ins-HA mice can activate low avidity KdHA-specific CD8+ T cells that are able to reject tumor cells expressing high levels of HA, yet these mice remain tolerant of pancreatic islet beta cells expressing HA. |
