Email updates

Keep up to date with the latest news and content from Retrovirology and BioMed Central.

This article is part of the supplement: AIDS Vaccine 2009

Open Access Poster presentation

P16-24. Crucial contribution of sub-dominant HLA-C allele restricted CTL responses to the control of HIV

J Ibarrondo1*, R Zúñiga2, M Farfán2, J Suarez2, B Mothe1, A Llano1, JJ Szinger3, W Hildebrand4, J Sánchez5, BT Korber3 and C Brander1

  • * Corresponding author: J Ibarrondo

Author Affiliations

1 HIVACAT, Fundació irsiCaixa, Badalona, Spain

2 Asociación Civil IMPACTA Salud y Educación, Lima, Peru

3 Los Alamos National Laboratory, Los Alamos, NM, USA

4 University of Oklahoma Medical Center, Oklahoma City, OK, USA

5 Investigaciones Médicas en Salud (INMENSA), Lima, Peru

For all author emails, please log on.

Retrovirology 2009, 6(Suppl 3):P253  doi:10.1186/1742-4690-6-S3-P253

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/6/S3/P253


Published:22 October 2009

© 2009 Ibarrondo et al; licensee BioMed Central Ltd.

Background

HLA-A and -B alleles have been associated with relative control of HIV disease and specific HLA-B restricted CTL responses have been implicated with effective antiviral activity. Despite recent reports finding genomic associations between the C locus and relative HIV control, little is know regarding HLA-C restricted CTL responses to HIV and their ability to facilitate viral control.

Methods

In a cohort of 248 HIV infected individuals from Peru, we determined the breath, magnitude and specificity of dominant and sub-dominant HLA-C restricted immune responses using an overlapping peptide set spanning the entire viral clade B HIV proteome.

Results

After correction for linkage disequilibrium with other HLA class I alleles, HLA-C alleles showed a wide range of relative protection from HIV disease progression, with HLA-C07, C08 and C17 alleles being associated with relative viral control while HLA-C04 was associated with high viral loads and low CD4 counts independently of HLA-B35 co-expression. Assessing ''break-through'' individuals, i.e. subjects who failed to control in vivo viral replication despite expressing one of the protective HLA-C alleles, indicate that relative control is in at least some cases mediated by sub-dominant T cell responses to HLA-C restricted epitopes.

Conclusion

These analyses strongly suggest that HLA-C restricted immune responses should be considered for HIV vaccine immunogen design, particularly also in the light of recent data indicating potentially synergistic effects of HLA-C restricted epitopes and recognition by NK cells.