Dong, T

Gillespie, G

Kessler, B

Kramer, H

McMichael, A

Ranasinghe, S

Rowland-Jones, S

Wright, C

Zhang, Y

English

PubMed

S Ranasinghe

H Kramer

C Wright

B Kessler

Y Zhang

G Gillespie

S Rowland-Jones

A McMichael

T Dong

Crossref

P17-28 LB. The antiviral efficacy of HIV-specific CD8+ T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate

Rowland-Jones S

Gillespie G

Zhang Y

Kessler B

Wright C

Kramer H

Ranasinghe S

McMichael A

Dong T

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Retrovirology
Open AccessPoster presentation
P17-28 LB. The antiviral efficacy of HIV-specific CD8+ T-cells to a 
conserved epitope is heavily dependent on the infecting HIV-1 
isolate
S Ranasinghe, H Kramer, C Wright, B Kessler, Y Zhang, G Gillespie, 
S Rowland-Jones, A McMichael and T Dong*
Address: Oxford University, Oxford, UK
* Corresponding author    
Background
The greatest challenge to developing an effective T-cell
based vaccine against HIV-1 is its high genetic variability.
We hypothesised that efficient CTL antiviral activity is not
only dependent on conserved epitopes but is also heavily
modulated by the infecting HIV strain, with virus specific
polymorphisms altering the efficiency of antigen process-
ing and presentation.
Methods
CTL Lysis Assays, ELISPOT assay, Live Virus ELISPOT
(LVE), Viral Suppression Assay (VSA), Intracellular Anti-
gen Processing Inhibition Assay (IAPIA) and Proteasomal
Digestion Assay (PDA) were used.
Results
We examined whether an invariant HLA-B8 restricted
Nef90-97 epitope FL8 shared between five high titre
viruses and eight recombinant vaccinia viruses expressing
Nef from different viral isolates (clades A-H) could acti-
vate antiviral activity in FL8-specific cytotoxic T-lym-
phocytes (CTL). Surprisingly, despite epitope
conservation, we found that CTL antiviral efficacy is heav-
ily dependent on the infecting viral strain. Only a small
proportion of HIV strains tested were correctly processed,
whilst 77% were impaired or abolished. This occurred
independently of clade-grouping and was associated with
virus-specific polymorphisms in the epitope flanking
region altering patterns of immunoproteasomal cleavage,
to increase or inhibit epitope generation.
Conclusion
we demonstrate that CTL antiviral efficacy to this con-
served immunodominant epitope is impaired in a strik-
ingly high proportion of viral isolates. These findings have
implications for evaluating the antiviral efficacy of domi-
nant T-cell responses in patients and the effectiveness of
vaccine-induced T-cells.
from AIDS Vaccine 2009
Paris, France. 19-22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P410 doi:10.1186/1742-4690-6-S3-P410
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts - A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P410
© 2009 Ranasinghe et al; licensee BioMed Central Ltd. 


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P17-28 LB. The antiviral efficacy of HIV-specific CD8+ T-cells to a conserved epitope is heavily dependent on the infecting HIV-1 isolate

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