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Volume 6 Supplement 3

AIDS Vaccine 2009

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


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.


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.


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.


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.

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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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Ibarrondo, J., Zúñiga, R., Farfán, M. et al. P16-24. Crucial contribution of sub-dominant HLA-C allele restricted CTL responses to the control of HIV. Retrovirology 6 (Suppl 3), P253 (2009).

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