Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes
Xue-Feng Bai, … , Pan Zheng, Yang Liu
Xue-Feng Bai, … , Pan Zheng, Yang Liu
Published May 15, 2003
Citation Information: J Clin Invest. 2003;111(10):1487-1496. https://doi.org/10.1172/JCI17656.
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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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Peptide binding to H-2Ld. After overnight incubation with β2-microglobul...
Peptide binding to H-2Ld. After overnight incubation with β2-microglobulin and given concentrations of peptides, H-2Ld–transfected RMA-S cells were stained with H-2Ld–specific mAb. (a) Representative FACS histograms. Numbers in the panels are mean fluorescence intensities. (b) Quantitative comparison of peptide:H-2Ld interaction. Data shown are representative of two to four independent experiments. Statistical significance was determined by paired t test. Med, medium.