P16-24. Crucial contribution of sub-dominant HLA-C allele restricted CTL responses to the control of HIV
Retrovirology volume 6, Article number: P253 (2009)
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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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). https://doi.org/10.1186/1742-4690-6-S3-P253