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- Variants of Gag, Env, and Nef epitopes were studied in one subject over >10 years of infection. A set of known HLA A*0201- and B*0702-restricted epitopes, plus additional predicted epitopes, was assembled. Epitope and variant responses were studied from 4 timepoints post-seroconversion (SC): early infection post-SC (0-2.8 yrs), late infection post-SC (3.25-7.8 yrs), early ART treatment (8.3-10.1 yrs), and late ART treatment. Despite evolutionary changes, CD8+ T cells could still be primed to HIV-1 variants. The percent of epitope variants inducing HIV-1-specific memory T cell responses peaked early post-SC, then declined and remained minimal shortly after establishment of viral set point. Peptide variants with medium binding affinity were more frequent than variants with low or high binding affinity but variants with different MHC class I binding capabilities induced equally broad memory T cell responses. A trimodal pattern in the breadth of T cell memory was seen, at early SC before viral set point, and then two peaks during later infection prior to commencing cART.
- SLFNTVATL was 1 of 7 epitopes with a positive correlation between predicted and observed MHC affinity. SLFNTVATL had a pattern of transient changes in the dominance of variants, with the founder variant eventually being more dominant. T-cell memory responses to SLFNTVATL were detected early post-SC, late post-SC, and during early ART treatment.
Nada M Melhem, Kellie N. Smith, Xiao-Li Huang, Bonnie A Colleton, Weimin Jiang, Robbie B. Mailliard, James I. Mullins, and Charles R. Rinaldo. The Impact of Viral Evolution and Frequency of Variant Epitopes on Primary and Memory Human Immunodeficiency Virus Type 1-Specific CD8+ T Cell Responses. Virology, 450-451:34-48, Feb 2014. PubMed ID: 24503065.
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