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De Novo Generation of Escape Variant-Specific CD8+ T-Cell Responses following Cytotoxic T-Lymphocyte Escape in Chronic Human Immunodeficiency Virus Type 1 Infection.
- Source :
-
Journal of Virology . Oct2005, Vol. 79 Issue 20, p12952-12960. 9p. 2 Diagrams, 3 Charts, 2 Graphs. - Publication Year :
- 2005
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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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 79
- Issue :
- 20
- Database :
- Academic Search Index
- Journal :
- Journal of Virology
- Publication Type :
- Academic Journal
- Accession number :
- 18536959
- Full Text :
- https://doi.org/10.1128/JVI.79.20.12952-12960.2005