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.
Bai
Xue-Feng
XF
Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, Ohio 43210, USA.
Liu
Jinqing
J
Li
Ou
O
Zheng
Pan
P
Liu
Yang
Y
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