Role of cytotoxic T-lymphocyte-mediated immune selection in a dominant human leukocyte antigen-B8-restricted cytotoxic T-lymphocyte epitope in Nef
| Autor: | Matthias Schmitt-Haendle, Katja Maurer, Ellen G. Harrer, Silke Bergmann, Sandra M. Mueller, Bernd M. Spriewald, Kathrin Eismann, Thomas Harrer, Andreas Goldwich |
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| Rok vydání: | 2008 |
| Předmět: |
Molecular Sequence Data
Epitopes T-Lymphocyte Viremia Human leukocyte antigen Biology Virus Epitope HLA-B8 Antigen medicine Cytotoxic T cell Humans Pharmacology (medical) Longitudinal Studies nef Gene Products Human Immunodeficiency Virus Acquired Immunodeficiency Syndrome Base Sequence Immunodominant Epitopes ELISPOT virus diseases T lymphocyte Middle Aged Viral Load medicine.disease Virology CD4 Lymphocyte Count CTL Infectious Diseases Immunology Mutation Female T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of acquired immune deficiency syndromes (1999). 48(2) |
| ISSN: | 1525-4135 |
| Popis: | Objectives: To study the role of cytotoxic T-lymphocyte (CTL) escape for disease progression in HIV-1 infection, we analyzed the CTL response to the dominant human leukocyte antigen (HLA)-B8-restricted CTL epitope FLKEKGGL (FL8) in HIV-1 Nef. Methods: HIV-1 nef genes derived from 56 patients were analyzed by polymerase chain reaction (PCR)-based sequencing. T-cell responses against FL8 and mutated FL8 variants were detected by γ-interferon (γ-IFN) enzyme linked immunospot (ELISPOT) assay. Results: The longitudinal analysis of an HIV-1-infected patient with good control of HIV-1 viremia for several years demonstrated an association of rising viremia with the emergence of CTL escape mutations within the HLA-B8-restricted Nef-specific CTL epitopes FLKEKGGL and WPAIRERM. Analysis of nef genes in 56 HIV-1-infected patients demonstrated a significant correlation between the occurrence of mutations in the FL8 epitope and the presence of HLA-B8. The mutations within the FL8 epitope could decrease CTL recognition; however, there was strong variation regarding the recognition of viral variants between individual donors. The presence of FL8 mutations was associated with lower CD4 cell counts and higher viral loads. Conclusions: Our data demonstrate a strong CTL selection pressure on the immunodominant HLA-B8-restricted CTL epitope FL8 in HIV-1 Nef. The association of FL8 mutations with lower CD4 cell counts indicates an important role of CTL escape mutations for disease progression. |
| Databáze: | OpenAIRE |
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