Volume 6 Supplement 3

AIDS Vaccine 2009

Open Access

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
Retrovirology20096(Suppl 3):P253


Published: 22 October 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.

Authors’ Affiliations

HIVACAT, Fundació irsiCaixa
Asociación Civil IMPACTA Salud y Educación
Los Alamos National Laboratory
University of Oklahoma Medical Center
Investigaciones Médicas en Salud (INMENSA)


© Ibarrondo et al; licensee BioMed Central Ltd. 2009

This article is published under license to BioMed Central Ltd.