Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes
Xue-Feng Bai, Jinqing Liu, Ou Li, Pan Zheng, Yang Liu
Xue-Feng Bai, Jinqing Liu, Ou Li, Pan Zheng, Yang Liu
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Article Oncology

Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes

Abstract

It is established that mutations in viral antigenic epitopes, or antigenic drifts, allow viruses to escape recognition by both Ab’s and T lymphocytes. It is unclear, however, whether tumor cells can escape immune recognition via antigenic drift. Here we show that adoptive therapy with both monoclonal and polyclonal transgenic CTLs, specific for a natural tumor antigen, P1A, selects for multiple mutations in the P1A antigenic epitope. These mutations severely diminish T cell recognition of the tumor antigen by a variety of mechanisms, including modulation of MHC:peptide interaction and TCR binding to MHC:peptide complex. These results provide the first evidence for tumor evasion of T cell recognition by antigenic drift, and thus have important implications for the strategy of tumor immunotherapy.

Authors

Xue-Feng Bai, Jinqing Liu, Ou Li, Pan Zheng, Yang Liu

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Mutations in the P1A epitope abolished or drastically reduced T cell rec...
Mutations in the P1A epitope abolished or drastically reduced T cell recognition of the antigen. (a) The AA sequences of the peptides used in the study, with the altered AA shown in bold. (b) Proliferation of transgenic T cells in response to either wild-type or mutant P1A peptide. (c) Cytolysis of P388D1 target cells pulsed with given concentrations of wild-type, mutant, or unrelated control H-2Ld–binding peptides. E/T = 10. (d) P1A mutants lack antagonistic activity for the P1CTL. Activated P1A-specific T cells were used as effectors. The target cells were preincubated with a mixture of wild-type P1A (10 ng/ml) and the indicated concentrations of mutant or wild-type P1A or control peptides. E/T = 10. Data shown were from a 6-hour 51Cr-release assay and are representative of three to five independent experiments. Ctrl, control.