Context-dependent immunogenicity of an S206G-substituted H-2Db-restricted simian virus 40 large T antigen epitope I variant.
SV40 large tumor Ag (Tag) contains four H-2b-restricted (I, II/III, IV, and V) CTL epitopes. A hierarchy exists among these CTL epitopes. CTL directed against epitopes I, II/III, and IV are readily detected following immunization of H-2b mice with SV40, Tag-transformed syngeneic cells, or a vaccinia recombinant that expresses full-length Tag, while epitope V-specific CTL are not. The mechanisms that define this hierarchy remain unknown. Initial studies have shown that the locations of epitopes I and V within SV40 Tag do not determine the immunological potencies of these epitopes. Like the wild-type Tag, derivatives in which the locations of epitopes I and V were precisely reversed within Tag failed to induce epitope V-specific CTL, but did induce epitope I-specific CTL. The use of an S206G-substituted epitope I variant (GAINNYAQKL) revealed that the S206G variant sequence induced CTL when located within the native epitope I context, but failed to do so when located within the epitope V context of Tag. Mutagenesis of residues adjacent to the S206G-substituted epitope I variant revealed that the identity of the residue flanking the amino terminus of the S206G variant was critical when it resided within the epitope V location, but not within the epitope I location. These results demonstrate that effects imposed by both regional context and adjacent residues can modulate immunogenicity, but that the relative importance of such effects varies in an epitope-dependent manner.
Mylin
L M
LM
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey 17033, USA. lmm19@psu.edu
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics* / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D000957:Antigens, Viral, Tumor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014644:Genetic Variation / Q000276:immunology; D005998:Glycine / Q000235:genetics* / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D012694:Serine / Q000235:genetics* / Q000276:immunology; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism