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Abstract
LONGITUDINAL INTERPLAY OF CD8+ T-CELL RESPONSES AND THE HIV-1 DERIVED P17 EPITOPE THEY RECOGNIZE DURING CHRONIC HIV-1 INFECTION
JAMIESON B, YANG O, HULTIN L, ALTMAN J, KORBER B, GIORGI J, WOLINSKY S
CTL are important for the control of HIV-1 infection, yet they usually fail to adequately suppress the virus. Exhaustion of CTL subsets and mutations in defined CTL epitopes have been postulated as mechanisms by which HIV-1 escapes from CTL. To further investigate these mechanisms we measured CD8+ T-cell responses to the gag epitope SLYNTVATL (SL9) during chronic HIV-1 infection by peptide-HLA tetramer and intracellular IFN-g staining over time. To phenotype responding subsets, tetramer-binding cells were stained for their maturation and activation status and for co-stimulatory molecules. Epitope mutation was measured in parallel by cloning and DNA sequencing of gag RNA from plasma. In 3/5 individuals tetramer binding was associated with the presence of wild-type SL9 sequences. Approximately 50-60% of these cells in all 3 individuals were functionally responsive, as measured by the expression of IFN-g. In 2/3 individuals tetramer binding was lost in parallel with mutations within SL9. In the remaining individual, wild-type SL9 sequences persisted for six years before finally exhibiting a single sequence mutation. It is unclear whether SL9-tetramer binding CTL were lost prior to, or concurrently with, the sequence mutation. In this individual, the tetramer response peaked at approximately half of the frequency observed in the other two individuals and the responding cells demonstrated a different phenotype defined by CD45RA and CD28. This individual was heterozygous for the SL9-presenting HLA allele, while the other two individuals were homozygous. In conclusion, our data support epitope sequence mutation as a means of viral escape from CTL and document that the failure of CTL to adequately control viral replication may also be a function of eliciting suboptimal CTL responses to immunodominant epitopes in some individuals. Understanding the reasons behind the diversity of the responses to these epitopes may help us understand how to augment CTL responses to HIV.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
78
Suggested Citation
"JAMIESONB, et al.
LONGITUDINAL INTERPLAY OF CD8+ T-CELL RESPONSES AND THE HIV-1 DERIVED P17 EPITOPE THEY RECOGNIZE DURING CHRONIC HIV-1 INFECTION.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
78"
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