Diversity of escape variant mutations in Simian virus 40 large tumor antigen (SV40 Tag) epitopes selected by cytotoxic T lymphocyte (CTL) clones

• Published in: Virology (New York, N.Y.) Vol. 364; no. 1; pp. 155 - 168
• Main Authors: Mylin, Lawrence M, Schell, Todd D, Epler, Melanie, Kusuma, Caroline, Assis, David, Matsko, Chelsea, Smith, Alexandra, Allebach, April, Tevethia, Satvir S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.07.2007
• Subjects: Amino Acid Sequence; Animals; Antigens, Polyomavirus Transforming - genetics; Antigens, Polyomavirus Transforming - immunology; Base Sequence; CD8+ T lymphocyte; Cell Line, Transformed; CTL clone; CTL epitope; CTL escape variant; Cytotoxicity; DNA, Viral - genetics; Epitope mutation; Epitopes - genetics; Genetic Variation; Immunity, Cellular; In Vitro Techniques; Infectious Disease; Mice; Mutation; Simian virus 40; Simian virus 40 - genetics; Simian virus 40 - immunology; SV40 Tag; T-Lymphocytes, Cytotoxic - immunology; SV40 Tag; CD8+ T lymphocyte; Epitope mutation; CTL epitope; Cytotoxicity; CTL escape variant; CTL clone
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2007.02.007

Abstract To better understand the relationship between epitope variation and tumor escape from immune surveillance, SV40 T antigen-transformed B6/K-0 cells were subjected to selection with individual CTL clones specific for the SV40 T antigen H-2Db -restricted epitopes I or V. CTL-resistant populations were isolated from a majority of the selection cultures and substituted epitope sequences were identified within most of the resistant populations. Tag sequences deleted of all or portions of the selection-targeted epitope were identified, but in lower numbers compared to epitope sequences bearing single residue substitutions. Relatively few flanking residue substitutions were identified, and only in epitope I-targeted selections. The diversity (numbers and epitope residue locations) of substituted epitope residue positions varied between selections. These findings suggest that the scope of spontaneously occurring mutations that could allow for escape from individual CD8+ T cell clones is large.