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Vogel, Thorsten U.; Friedrich, Thomas C.; O'Connor, David H.; Rehrauer, William; Dodds, Elizabeth J.; Hickman, Heather; Hildebrand, William; Sidney, John; Sette, Alessandro; Hughes, Austin; Horton, Helen; Vielhuber, Kathy; Rudersdorf, Richard; de Souza, Ivna P.; Reynolds, Matthew R.; Allen, Todd M.; Wilson, Nancy; Watkins, David I.

Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?

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  • Medientyp: E-Artikel
  • Titel: Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?
  • Beteiligte: Vogel, Thorsten U.; Friedrich, Thomas C.; O'Connor, David H.; Rehrauer, William; Dodds, Elizabeth J.; Hickman, Heather; Hildebrand, William; Sidney, John; Sette, Alessandro; Hughes, Austin; Horton, Helen; Vielhuber, Kathy; Rudersdorf, Richard; de Souza, Ivna P.; Reynolds, Matthew R.; Allen, Todd M.; Wilson, Nancy; Watkins, David I.
  • Erschienen: American Society for Microbiology, 2002
  • Erschienen in: Journal of Virology
  • Sprache: Englisch
  • DOI: 10.1128/jvi.76.22.11623-11636.2002
  • ISSN: 0022-538X; 1098-5514
  • Schlagwörter: Virology ; Insect Science ; Immunology ; Microbiology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>ABSTRACT</jats:title><jats:p>It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag<jats:sub>71-79</jats:sub>GY9), and one from the Nef protein (Nef<jats:sub>159-167</jats:sub>YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef<jats:sub>159-167</jats:sub>YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag<jats:sub>71-79</jats:sub>GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat<jats:sub>28-35</jats:sub>SL8, which reproducibly selects for escape variants during acute infection, and Gag<jats:sub>181-189</jats:sub>CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection.</jats:p>
  • Zugangsstatus: Freier Zugang