Simian immunodeficiency virus evades a dominant epitope-specific cytotoxic T lymphocyte response through a mutation resulting in the accelerated dissociation of viral peptide and MHC class I

Zheng W. Chen, Abie Craiu, Ling Shen, Marcelo J. Kuroda, Ugonna C. Iroku, David I. Watkins, Gerald Voss, Norman L. Letvin

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The ability of an AIDS virus to escape from immune containment by selective mutation away from recognition by CTL was explored in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. CTL recognition of a previously defined common vital mutation in an immunodominant SIVmac Gag epitope was evaluated. CTL were assessed for their ability to recognize a SIVmac Gag protein with a single residue 2 (T → A) replacement in the minimal epitope peptide bound by the MHC class I molecule Mamu-A*01+. SIVmac Gag-specific CTL lysed Mamu-A*01+ target cells infected with recombinant vaccinia virus expressing the wild-type but not the mutant Gag protein. In addition, CTL recognized the mutant epitope peptide less efficiently than the wild-type virus peptide. In studies to determine the mechanism by which the mutant virus evaded CTL recognition, this peptide was shown to bind Mamu-A*01 in a manner that was indistinguishable from the wild-type peptide. However, experiments in which an increasing duration of delay was introduced between peptide sensitization of target cells and the assessment of these cells as targets in killing assays suggest that the mutant peptide with a T → A replacement had a higher off-rate from Mamu- A*01 than the wild-type peptide did. Therefore, these findings suggest that AIDS viruses can evade virus-specific CTL responses through the accelerated dissociation of mutant peptide from MHC class I.

Original languageEnglish (US)
Pages (from-to)6474-6479
Number of pages6
JournalJournal of Immunology
Volume164
Issue number12
DOIs
StatePublished - Jun 15 2000
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Simian immunodeficiency virus evades a dominant epitope-specific cytotoxic T lymphocyte response through a mutation resulting in the accelerated dissociation of viral peptide and MHC class I'. Together they form a unique fingerprint.

  • Cite this