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Volume 9 Supplement 2

AIDS Vaccine 2012

  • Poster presentation
  • Open Access

KIR-HLA footprints and NK cell-mediated recognition of HIV-1

  • 1,
  • 2,
  • 1,
  • 3,
  • 1,
  • 4,
  • 3,
  • 5,
  • 2,
  • 3 and
  • 1
Retrovirology20129 (Suppl 2) :P170

https://doi.org/10.1186/1742-4690-9-S2-P170

  • Published:

Keywords

  • Logistic Regression Analysis
  • Infected Cell
  • Population Level
  • Infected Individual
  • Binding Study

Background

Increasing data suggest an important role of KIR+ NK cells in the control of HIV-1, however the precise mechanisms on how NK cells recognize HIV-1-infected cells remain poorly understood. KIRs can bind to HLA class I molecules, but the binding affinity of these interactions is dependent on the HLA class I presented epitope. Recent reports have suggested that sequence variations within HIV-1 epitopes presented by HLA class I can affect the binding of inhibitory KIRs expressed on NK cells, potentially modulating NK cell responses to infected cells. Here we investigated whether HIV-1 might adapt to the combined KIR/HLA genotypes on a population level to identify areas within HIV-1 that might be targeted by KIR+ NK cells.

Methods

HIV-1 Gag was sequenced in 390 untreated chronically clade C infected individuals from KwaZulu-Natal, South Africa. All study subjects were HLA class I and KIR typed. Phylogenetically-corrected logistic regression analysis of KIR/HLA associated Gag sequence polymorphisms was performed and q-values were used for multiple test correction.

Results

A total of 93 sequence polymorphisms significantly associated with the combined HLA/KIR genotypes were identified (p<0.05), 6 of them with a false-positive rate of less than 20% (q<0.2). These significant associations were independent of previously identified KIR or HLA-linked polymorphisms.

Conclusion

This study identified several sequence polymorphisms within HIV-1 Gag that were significantly associated with the expression of combined KIR/HLA genotypes at the population level, indicating adaptation of HIV-1 to NK cell mediated immune pressure. KIR/HLA class I binding studies in the context of the sequence polymorphisms and studies for NK cell function are ongoing to determine the consequence of these sequence changes for NK cell-mediated recognition of HIV-1-infected cells.

Authors’ Affiliations

(1)
University of KwaZulu-Natal, Durban, South Africa
(2)
Microsoft Research, Redmond, WA, USA
(3)
Ragon Institute of MIT, MGH and Harvard, Boston, MA, USA
(4)
University of Oxford, Oxford, UK
(5)
Cancer and Inflammation Program, Laboratory of Experimental Immunology, Frederick, MD, USA

Copyright

© Thobakgale 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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