11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retrovir Opportunistic Infect 2004 Feb 8-11; 11:(abstract no. 12)

R Draenert¹, T M Allen¹, G Sirera², C L Verrill¹, R Eldridge¹, L Ruiz², B D Walker¹, and J Martinez-Picado^2
1Partners AIDS Res. Ctr., Boston, MA, USA and ²Fndn. IrsiCaixa, Barcelona, Spain

BACKGROUND: CD8⁺ T-cell responses have been shown to contribute to control in HIV-1 infection. Viral escape from these responses has been well described but the effect of this phenomenon on control remains poorly understood. Experiments in the human setting are usually limited by many variables that cannot be controlled for as they can in animal studies. Here we present longitudinal follow-up of CD8 T-cell responses and viral escape in identical twins who were infected with the same virus at the same time. The results are compared with a third sibling who shares half of the twins' HLA alleles and who was infected with their virus 1.5 years later.

METHODS: We screened comprehensively for CD8⁺ T-cell responses with overlapping peptides spanning all HIV proteins by INF-γ ELISpot assay using fresh or frozen PBMC. Sequencing of targeted epitopes was performed on viral RNA or proviral DNA. Novel HLA-class-I epitopes were mapped in the regions of interest.

RESULTS: The clinical disease course over 2.5 years in both twins was comparable with CD4 counts of 250 to 500 cells/(L and viral loads of 10,000 to 30,000 copies/mL in the absence of HAART. We detected 22 different CD8 T-cell responses. When followed longitudinally, 10 of the CD8 T-cell responses were stable or increased in both, 5 decreased in both, and 7 showed differences between the twins over the disease course. HLA-B4001 is the immunodominant allele with 4 strong responses restricted by this allele in early infection. Viral escape was observed in 3 of these epitopes in parallel in both twins with the same amino acid change. The third brother shares the B4001 allele and fails to make a response to the B4001 epitope that escaped before transmission. However, he does make responses to the other 3 B4001 epitopes. Despite this similarity, viral evolution also occurred with differences between the twins.

CONCLUSIONS: This setting shows that although the majority of CD8 T-cell responses are similar, with viral escape developing in parallel, responses and viral evolution differ. This implies that the genetic background is a major determinate for CD8 T-cell responses, but other factors play a role as well. These results are important for understanding HIV pathogenesis and for vaccine development.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.