| First Author | Lotz C | Year | 2004 |
| Journal | Int J Cancer | Volume | 108 |
| Issue | 4 | Pages | 571-9 |
| PubMed ID | 14696122 | Mgi Jnum | J:88318 |
| Mgi Id | MGI:3032801 | Doi | 10.1002/ijc.11602 |
| Citation | Lotz C, et al. (2004) Partial tyrosinase-specific self tolerance by HLA-A*0201-restricted cytotoxic T lymphocytes in mice and man. Int J Cancer 108(4):571-9 |
| abstractText | The human tyrosinase (hTyr) (369-377) cytotoxic T lymphocyte (CTL) epitope is presented by malignant melanoma and various nontransformed cells in association with human leukocyte antigen (HLA)-A*0201 (A2.1) and used for vaccination-based immunotherapy of melanoma patients. Its mouse homologue, mTyr (369-377), is naturally processed and bound by A2.1 with equivalent efficacy and thus enabled us to explore the effect of self tolerance on Tyr-specific T cells in different lines of A2.1 transgenic (Tg) mice and man. We found that self Tyr-reactive CTL in Tg mice and, importantly, in man were affected by partial tolerance resulting in only residual T lymphocytes of higher avidity for self Tyr along with low-avidity T cells to be present in the periphery. Immunizing mice with the xenogeneic nonself Tyr peptide facilitated the generation of self Tyr-reactive CTL. As compared to Tyr-reactive CTL induced by high amounts of the self Tyr epitope, however, the nonself antigen (Ag) had no effect on improving the avidity of self Tyr-specific mouse and human T cells. Depleting mice of CD25(+) T cells with and without CTL-associated Ag 4 (CTLA-4) blockade demonstrated that tolerance of Tyr-specific CTL was not regulated by CD4(+)CD25(+) T regulatory cells (Treg) or CTLA-4. Our studies have important implications for the design of anti-Tyr-based immunotherapeutics. |
