Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

HIV control through a single nucleotide on the HLA-I locus

  • H Kløverpris1,
  • M Harndahl2,
  • J Carlson1,
  • A Leslie1,
  • M van der Stok3,
  • G Huang1,
  • F Chen4,
  • L Riddell5,
  • D Steyn6,
  • D Goedhals6,
  • C van Vuuren6,
  • J Frater1,
  • B Walker7,
  • T Ndung'u'3,
  • S Buus2 and
  • P Goulder1
Retrovirology20129(Suppl 2):O47

https://doi.org/10.1186/1742-4690-9-S2-O47

Published: 13 September 2012

Background

In correlative studies HLA class I type is consistently found to have the strongest impact on HIV disease progression. However, the exact mechanism involved is complicated by several factors; many alleles are ligands for NK cells as well as CD8 T-cells, and strong linkage disequilibrium between Class I alleles makes it difficult to distinguish the effect of individual alleles from other HLAs or from other important loci found on the HLA haplotype, such as the recently described -35 SNP.

Methods

Here we study two recently diverged HLA alleles, B*4201 and B*4202, which only differ by a single amino acid. Crucially, they occur primarily on identical Class I haplotypes and do not act as NK cell ligands. Therefore, they represent a unique opportunity to study the impact of a single HLA allele on HIV immune control not confounded by other genetic factors in a large outbred cohort (n=2,093) of C-clade infected individuals.

Results

Here we show that the amino acid change in position 9 of the HLA-B molecule, is critical for peptide binding and significantly alters the Gag CTL epitopes targeted (P=2x10-10), measured both directly ex-vivo by ELISPOT and indirectly through CTL escape mutation (P=2x10-8). Strikingly, HLA-B*4201 is associated with significantly lower viral load setpoint than HLA-B*4202 (P=0.02).

Conclusion

This naturally controlled experiment represents perhaps the clearest demonstration of the direct impact of particular HIV Gag specific CTL on disease control.

Authors’ Affiliations

(1)
University of Oxford
(2)
University of Copenhagen
(3)
University of KwaZulu-Natal
(4)
Royal Berkshire Hospital
(5)
Northampton General Hospital
(6)
University of Free State
(7)
Ragon Institute of MGH, MIT and Harvard

Copyright

© Kløverpris 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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