| First Author | Hernández J | Year | 2000 |
| Journal | J Immunol | Volume | 164 |
| Issue | 2 | Pages | 596-602 |
| PubMed ID | 10623800 | Mgi Jnum | J:59295 |
| Mgi Id | MGI:1351360 | Doi | 10.4049/jimmunol.164.2.596 |
| Citation | Hernandez J, et al. (2000) The use of HLA A2.1/p53 peptide tetramers to visualize the impact of self tolerance on the TCR repertoire. J Immunol 164(2):596-602 |
| abstractText | p53 is an attractive target for cancer immunotherapy since it is overexpressed in half of all tumors. However, it is also expressed in normal lymphoid tissue, and self tolerance leaves a p53-specific repertoire purged of high avidity CTL. To better understand the mechanism of tolerance and the basis for such low avidity interaction, p53-specific CTL from p53 deficient (p53-) and sufficient (p53+) A2.1/Kb transgenic mice were compared with respect to their ability to bind HLA-A2.1 tetramers containing cognate murine p53 peptide Ag, p53 261-269. Since the murine CD8 molecule cannot interact with human HLA-A2.1, this tests the ability of the TCR to bind the A2.1/peptide complex tetramer. CTL from p53- mice demonstrated strong binding of such A2.1/p53 261-269 tetramers; however, the CTL from tolerant p53+ mice were devoid of tetramer-binding CD8+ T cells. Examination of TCR expression at the clonal level revealed that CTL from p53+ and p53- mice each expressed comparable levels of the p53-specific TCR. These results indicate that normal expression of p53 promotes elimination of T cells expressing TCRs with sufficient affinity to achieve stable binding of the A2.1/p53 261-269 tetramers. |
