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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

HIV-1 p24 derived epitopes modulate KIR2DL2-binding to HLA-Cw03

  • 1,
  • 2,
  • 2,
  • 3,
  • 4,
  • 1 and
  • 2
Retrovirology20129 (Suppl 2) :P180

https://doi.org/10.1186/1742-4690-9-S2-P180

  • Published:

Keywords

  • Natural Killer Cell
  • Natural Killer Cell Receptor
  • Antiviral Function
  • Inhibitory Natural Killer Cell
  • Inhibitory KIRs

Background

Recent studies have suggested that HIV-1 can evade Natural Killer (NK)-cell-mediated immunity by mutating viral epitopes to enhance engagement of inhibitory Killer Ig-like receptors (KIRs) expressed on NK cells. However, the precise mechanisms modulating the interaction of inhibitory KIRs and their HLA class I ligands, and the role that HIV-1 epitopes might play in this interaction are not well understood. In this study we investigated whether HLA-Cw3-presented epitopes within HIV-1 p24 Gag can modulate binding of KIR2DL2, an inhibitory KIR, to HLA-Cw03.

Methods

Using tapasin-deficient 721.220 cell line expressing HLA-Cw*0304 we initially screened for HIV-1 peptides that stabilized HLA-Cw*0304 expression using 222 10-mer peptides overlapping by 9 amino acids spanning the entire HIV-1 p24 Gag sequence. Peptides stabalizing HLA-Cw*0304 expression were thereafter investigated for their ability to facilitate binding of a KIR2DL2-IgG fusion construct.

Results

We identified several HIV-1 p24 epitopes that were able to stabilize HLA–Cw*0304 expression. A subset of these epitopes also allowed for binding of KIR2DL2. Currently we are investigating the consequences of KIR2DL2-binding to HLA class I presented HIV-1 epitopes for the antiviral function of primary NK cells from KIR2DL2+ individuals.

Conclusion

Taken together, these studies have identified epitopes within HIV-1 that enhance the binding of the inhibitory NK cell receptor KIR2DL2 to its ligand HLA-Cw3, and are in line with recent data suggesting that the sequence of the HLA class I presented epitope has an important impact on the interaction between KIR and HLA class I (Boyington et al. Nature 2000, Vivian et al. Nature 2011).

Authors’ Affiliations

(1)
UMC Utrecht, Utrecht, the Netherlands
(2)
Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA
(3)
IrsiCaixa (Institut de Recerca de la Sida), Barcelona, Spain
(4)
National Cancer Institute at Frederick, Frederick, MD, USA

Copyright

© van Teijlingen et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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