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Volume 6 Supplement 3

AIDS Vaccine 2009

P08-05. Does increased expression of HLA-C allow better control of HIV-1 viral load?

Background

A polymorphism ~35 kb upstream of the HLA-C gene (the ''-35 SNP'') correlates with host control of HIV-1 in Caucasians: the minor allele (C) associates with lower set point viral loads than the major allele (T). A link between viral load and HLA-C is suggested by linkage of the two SNP alleles with different HLA-C alleles, and by the fact that HLA-C is not down-regulated by nef.

Methods

We are investigating whether the -35 SNP correlates with the surface level of HLA-C using the antibody DT9, which recognises both HLA-C and HLA-E. The contribution of HLA-E to this staining is being assessed with the HLA-E-specific antibody MEM-E/06, and saturation-binding experiments are being used to measure the relative levels of HLA-E and HLA-C. We are also investigating functional differences individuals homozygous for the protective (C/C) and non-protective (T/T) -35 alleles.

Results

DT9 staining of lymphocytes is significantly lower for T/T subjects compared with C/C subjects (p = 0.046), but this is due to HLA-Cw7. Staining of T/T individuals who are homozygous for Cw7 is significantly lower than for both C/C individuals (p = 0.004) and T/T individuals who do not have (or who are heterozygous for) Cw7 (p = 0.007). We see no difference in the frequency or magnitude of ex vivo T cell responses to HLA-C-restricted peptides between C/C and T/T HIV-infected subjects. Likewise, there is no difference in the ability of NK cells from C/C and T/T subjects to control the replication of HIV in vitro. T cell clones specific for HLA-C-restricted peptides are being generated to investigate if the efficiency of peptide presentation by antigen presenting cells correlates with the -35 SNP, and the interactions of NK cells with macrophages and dendritic cells are being addressed.

Conclusion

DT9 staining suggests that surface levels of HLA-C are only significantly lower for T/T subjects who are homozygous for HLA-Cw7.

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Correspondence to S Brackenridge.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://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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Brackenridge, S., Corrah, T., Haygreen, E. et al. P08-05. Does increased expression of HLA-C allow better control of HIV-1 viral load?. Retrovirology 6, P113 (2009). https://doi.org/10.1186/1742-4690-6-S3-P113

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Keywords

  • Peptide
  • Viral Load
  • Minor Allele
  • Antigen Present Cell
  • Cell Clone