- Poster presentation
- Open Access
Plasticity of HIV-specific CD8 T cell responses in untreated HIV-1 infection- a step towards a therapeutic vaccine against drug resistance mutations
© Roider et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Cell Response
- Viral Sequence
- Drug Resistance Mutation
- Untreated Subject
- Variant Epitope
For a therapeutic HIV-1 vaccine, it should be considered that the immune system has been confronted with a certain viral sequence and mounted CD8 T cell responses specifically towards the infecting virus. One question is whether the immune system of HIV-infected individuals can create a new response towards a variant epitope in the case of vaccination. To study this in a comparable setting, we addressed the question how frequently a new CD8 T cell response can be generated after the occurrence of a viral escape mutation in its recognized epitope in a population not selected for a certain HLA allele.
19 HIV-infected untreated subjects were sampled longitudinally (>6 months. We searched for CD8 T cell responses that declined over the course of untreated infection and sequenced the autologous virus of the early and late time point by RT-PCR. Recognition of wildtype and newly arising sequences was compared in peptide titration assays.
A total of 30 declining CD8 T cell responses were studied in detail and viral sequence analyses showed amino acid changes in 25 (83%) of these. Peptide titration assays revealed 12 (48%) viral escape mutations with 2 de-novo responses (17%). Here the de-novo response showed less effector functions than the original CD8 T cell response. In addition we identified 5 (20%) shifts in immunodominance. None of the subjects with adaptation to the changing virus carried the HLA alleles B27, B57 or B*5801.
Our results show that CD8 T cell responses can adapt to the mutations of HIV. However it was limited to only 28% (7 out of 25) of cases in a cohort not expressing protective HLA alleles.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.