Journal article
De Novo generation of escape Variant-specific CD8+ T-Cell responses following Cytotoxic T-Lymphocyte escape in chronic Human Immunodeficiency Virus Type 1 Infection
Journal of Virology, Vol.79(20), pp.12952-12960
2005
Abstract
Human immunodeficiency virus type 1 (HIV-1) evades CD8+ T-cell responses through mutations within targeted epitopes, but little is known regarding its ability to generate de novo CD8+ T-cell responses to such mutants. Here we examined gamma interferon-positive, HIV-1-specific CD8+ T-cell responses and autologous viral sequences in an HIV-1-infected individual for more than 6 years following acute infection. Fourteen optimal HIV-1 T-cell epitopes were targeted by CD8+ T cells, four of which underwent mutation associated with dramatic loss of the original CD8+ response. However, following the G357S escape in the HLA-A11-restricted Gag349-359 epitope and the decline of wild-type-specific CD8+ T-cell responses, a novel CD8+ T-cell response equal in magnitude to the original response was generated against the variant epitope. CD8+ T cells targeting the variant epitope did not exhibit cross-reactivity against the wild-type epitope but rather utilized a distinct T-cell receptor Vβ repertoire. Additional studies of chronically HIV-1-infected individuals expressing HLA-A11 demonstrated that the majority of the subjects targeted the G357S escape variant of the Gag349-359 epitope, while the wild-type consensus sequence was significantly less frequently recognized. These data demonstrate that de novo responses against escape variants of CD8+ T-cell epitopes can be generated in chronic HIV-1 infection and provide the rationale for developing vaccines to induce CD8+ T-cell responses directed against both the wild-type and variant forms of CD8 epitopes to prevent the emergence of cytotoxic T-lymphocyte escape variants.
Details
- Title
- De Novo generation of escape Variant-specific CD8+ T-Cell responses following Cytotoxic T-Lymphocyte escape in chronic Human Immunodeficiency Virus Type 1 Infection
- Authors/Creators
- T.M. Allen (Author/Creator)X.G. Yu (Author/Creator)E.T. Kalife (Author/Creator)L.L. Reyor (Author/Creator)M. Lichterfeld (Author/Creator)M. John (Author/Creator)M. Cheng (Author/Creator)R.L. Allgaier (Author/Creator)S. Mui (Author/Creator)N. Frahm (Author/Creator)G. Alter (Author/Creator)N.V. Brown (Author/Creator)M.N. Johnston (Author/Creator)E.S. Rosenberg (Author/Creator)S.A. Mallal (Author/Creator)C. Brander (Author/Creator)B.D. Walker (Author/Creator)M. Altfeld (Author/Creator)
- Publication Details
- Journal of Virology, Vol.79(20), pp.12952-12960
- Publisher
- American Society for Microbiology
- Identifiers
- 991005545553807891
- Copyright
- 2005 American Society for Microbiology
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
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- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Virology
- ESI research areas
- Microbiology