Lack of strong immune selection pressure by the immunodominant, HLA- A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection

Christian Brander, Kelly E. Hartman, Alicja K. Trocha, Norman G. Jones, R. Paul Johnson, Bette Korber, Peggy Wentworth, Susan P. Buchbinder, Steven Wolinsky, Bruce D. Walker, Spyros A. Kalams*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

143 Scopus citations

Abstract

Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to vital load and viral sequence variation remains controversial. We analyzed HLA-A*0201 restricted cytotoxic T lymphocyte responses in 17 HIV-1-infected individuals with viral loads ranging from < 400 to 221,000 HIV RNA molecules per milliliter of plasma. In 13 out of 17 infected subjects, CTL responses against the SLYNTVATL epitope (p17 Gag; aa 77-85) were detectable, whereas two other HLA-A*0201 restricted epitopes (ILKEPVHGV, IV9; and VIYQYMDDL, VL9) were only recognized by six and five individuals out of 17 individuals tested, respectively. Naturally occurring variants of the SL9 epitope were tested for binding to HLA-A*0201 and for recognition by specific T cell clones generated from five individuals. Although these variants were widely recognized, they differed by up to 10,000-fold in terms of variant peptide concentrations required for lysis of target cells. A comparison of viral sequences derived from 10 HLA- A*0201-positive individuals to sequences obtained from 11 HLA-A*0201- negative individuals demonstrated only weak evidence for immune selective pressure and thus question the in vivo efficacy of immunodominant CTL responses present during chronic HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)2559-2566
Number of pages8
JournalJournal of Clinical Investigation
Volume101
Issue number11
DOIs
StatePublished - Jun 1 1998

Keywords

  • AIDS
  • Antigen processing
  • Escape
  • Immunodominance
  • Variant

ASJC Scopus subject areas

  • Medicine(all)

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