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

J Clin Invest. 2003 May;111(10):1487-96. doi: 10.1172/JCI17656.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics*
  • Antigens, Neoplasm / immunology*
  • Clone Cells / immunology
  • Clone Cells / pathology
  • DNA Mutational Analysis
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Disease Models, Animal
  • Epitopes / genetics
  • Epitopes / immunology
  • Genetic Drift*
  • Immunotherapy, Adoptive / adverse effects
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Plasmacytoma / immunology*
  • Plasmacytoma / pathology
  • Plasmacytoma / therapy
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / transplantation
  • Tumor Escape / genetics
  • Tumor Escape / immunology*


  • Antigens, Neoplasm
  • DNA-Binding Proteins
  • Epitopes
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • V(D)J recombination activating protein 2
  • tumor rejection antigen P815A, mouse