The role of proximal and distal sequence variations in the presentation of an immunodominant CTL epitope encoded by the ecotropic AK7 MuLV.
An emv-14-derived, replication-competent ecotropic murine leukemia virus [MuLV], designated AK7, was previously cloned from the AKXL-5 recombinant inbred mouse strain and partially characterized. While genetically encoding for an envelope-derived immunodominant CTL epitope [KSPWFTTL] located in the transmembrane region of p15TM, this virus, unlike the emv-11-derived virus AKR623, fails to be efficiently recognized by AKR/Gross MuLV-specific cytotoxic T lymphocytes [CTL]. AK7 thus provides the opportunity to study the role of retroviral sequence variations that are located outside of the immunodominant epitope as a mechanism of escape from CTL-mediated immune surveillance. In an attempt to identify which region[s] of the AK7 genome could account for its ability to evade efficient recognition by AKR/Gross MuLV-specific CTL, we have constructed recombinant murine retroviruses. The direct influence of a sequence variation twelve amino acids N-terminal to KSPWFTTL was explored with the use of chimeric viruses and determined not to significantly impair the presentation of KSPWFTTL to AKR/Gross MuLV-specific CTL. The long terminal repeat [LTR] derived from the AK7 virus, which possesses only one copy of the 99-base pair transcriptional enhancer in the U3 region, in contrast to AKR623 that possesses two copies of the tandem direct repeat enhancers, was also analyzed for its influence on the presentation of KSPWFTTL. Interestingly, our data indicate that the enhancer region derived from AK7 negatively influences the presentation of KSPWFTTL in the context of a recombinant AKR623 virus.
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Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire, USA.
Green
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D000406:AKR murine leukemia virus / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D004742:Enhancer Elements, Genetic; D016056:Immunodominant Epitopes / Q000235:genetics; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D017931:DNA Primers; D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins