Antigenic drift as a mechanism for tumor evasion of destruction by cytolytic T lymphocytes.
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.
Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Xue-Feng
XF
Bai
Jinqing
J
Liu
Ou
O
Li
Pan
P
Zheng
Yang
Y
Liu
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D004195:Disease Models, Animal; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D040961:Genetic Drift; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D010954:Plasmacytoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000637:transplantation; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000939:Epitopes; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2; C076546:tumor rejection antigen P815A, mouse