Efficient processing of the immunodominant, HLA-A*0201-restricted human immunodeficiency virus type 1 cytotoxic T-lymphocyte epitope despite multiple variations in the epitope flanking sequences

Christian Brander*, Otto O. Yang, Norman G. Jones, Yun Lee, Philip Goulder, R. Paul Johnson, Alicja Trocha, David Colbert, Christine Hay, Susan Buchbinder, Cornelia C. Bergmann, Hans J. Zweerink, Steven Wolinsky, William A. Blattner, Spyros A. Kalams, Bruce D. Walker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Immune escape from cytotoxic T-lymphocyte (CTL) responses has been shown to occur not only by changes within the targeted epitope but also by changes in the flanking sequences which interfere with the processing of the immunogenic peptide. However, the frequency of such an escape mechanism has not been determined. To investigate whether naturally occurring variations in the flanking sequences of an immunodominant human immunodeficiency virus type 1 (HIV-1) Gag CTL epitope prevent antigen processing, cells infected with HIV-1 or vaccinia virus constructs encoding different patient-derived Gag sequences were tested for recognition by HLA-A*0201-restricted, p17-specific CTL. We found that the immunodominant p17 epitope (SL9) and its variants were efficiently processed from minigene expressing vectors and from six HIV-1 Gag variants expressed by recombinant vaccinia virus constructs. Furthermore, SL9-specific CTL clones derived from multiple donors efficiently inhibited virus replication when added to HLA-A*0201-bearing cells infected with primary or laboratory-adapted strains of virus, despite the variability in the SL9 flanking sequences. These data suggest that escape from this immunodominant CTL response is not frequently accomplished by changes in the epitope flanking sequences.

Original languageEnglish (US)
Pages (from-to)10191-10198
Number of pages8
JournalJournal of virology
Volume73
Issue number12
DOIs
StatePublished - Dec 1999

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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