Heckerman, D

Lazaro, E

Le Gall, S

Martinez, S

Walker, BD

Zhang, M

Zhang, S

English

PubMed

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BioMed Central
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Retrovirology
Open AccessOral presentation
SO4-05 OA. The intracellular production of HIV antigenic peptides 
is guided by predictable motifs and can be altered: implications for 
immunogen design
E Lazaro2, S Zhang2, M Zhang2, S Martinez2, D Heckerman1, BD Walker2 and 
S Le Gall*2
Address: 1Microsoft Research, Seattle, WA, USA and 2Ragon Institute of MGH, MIT and Harvard, Harvard Medical School and Mass General 
Hospital, Boston, MA, USA
* Corresponding author    
Background
The success of a T cell-based vaccine relies not only on the
identification of protective epitopes but also on the capac-
ity of vaccinated tissues to produce and present these
epitopes to immune cells. Defining predictable events
leading to efficient epitope presentation is critical to
immunogen design. Epitopes are short protein fragments
escaping degradation, but factors controlling the effi-
ciency of epitope production are unknown. We previously
identified portable flanking sequences altering epitope
production and antigenicity. In order to define motifs
driving efficient epitope production, we analyzed the deg-
radation of long HIV peptides into shorter fragments as
well as the capacity of antigenic peptides to sustain intra-
cellular degradation.
Methods
We combined epitope processing assays with computa-
tional analysis of degradation products. Long HIV pep-
tides were incubated with PBMC extracts and degradation
fragments were identified by mass spectrometry. Addi-
tionally we measured the intracellular stability of 167 HIV
epitopes by HPLC profile analysis, where the surface of
the peak corresponding to one peptide is proportional to
the epitope amount. We performed a computational anal-
ysis of peptides resistant or sensitive to degradation.
Finally we introduced stability or degradation motifs in
peptides and measured the stability of mutated sequences.
Results
The analysis of hundreds of degradation fragments identi-
fied 36 motifs enriched in fragments and absent in cleav-
age sites. We also demonstrate a great heterogeneity in
intracellular epitope stability (half-lives: 210 ms–39 min).
We identified 14 motifs associated with intracellular sta-
bility and 21 with rapid degradation of epitopes. Intro-
ducing stability motifs into unstable peptides increased
stability by 9-fold whereas mutating these motifs in stable
peptides decreased stability by up to 100-fold.
Conclusion
This is the first definition of rules driving the production
of antigenic peptides. These data suggest that epitope
processing from HIV immunogens could be manipulated
so as to enhance production of protective epitopes and
increase intracellular degradation of non-protective
epitopes.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):O47 doi:10.1186/1742-4690-6-S3-O47
<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/O47
© 2009 Lazaro et al; licensee BioMed Central Ltd. 


SO4-05 OA. The intracellular production of HIV antigenic peptides is guided by predictable motifs and can be altered: implications for immunogen design

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SO4-05 OA. The intracellular production of HIV antigenic peptides is guided by predictable motifs and can be altered: implications for immunogen design

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