Epitope Escape Mutation and Decay of Human Immunodeficiency Virus Type 1-Specific CTL Responses

Beth D. Jamieson*, Otto O. Yang, Lance Hultin, Mary Ann Hausner, Patricia Hultin, Jose Matud, Kevin Kunstman, Scott Killian, John Altman, Kristina Kommander, Bette Korber, Janis Giorgi, Steven Wolinsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

To investigate possible mechanisms behind HIV-1 escape from CTL, we performed detailed longitudinal analysis of Gag (SLYNTVATL)- and RT (ILKEPVHGV)-specific CTL responses and plasma epitope sequences in five individuals. Among those with CTL against consensus epitope sequences, epitope mutations developed over several years, invariably followed by decay of the CTL targeting the consensus epitopes. The maturation state of the CTL varied among individuals and appeared to affect the rate of epitope mutation and CTL decay, despite similar IFN-γ production. Escape mutations were oligoclonal, suggesting fitness constraints. The timing of escape indicated that the net selective advantage of escape mutants was slight, further underscoring the importance of understanding factors determining selective pressure and viral fitness in vivo. Our data show surprisingly consistent decay of CTL responses after epitope escape mutation and provide insight into potential mechanisms for both immune failure and shifting CTL specificities.

Original languageEnglish (US)
Pages (from-to)5372-5379
Number of pages8
JournalJournal of Immunology
Volume171
Issue number10
DOIs
StatePublished - Nov 15 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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