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Altering effects of antigenic variations in HIV-1 on antiviral effectiveness of HIV-specific CTLs.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 May 01; Vol. 178 (9), pp. 5513-23. - Publication Year :
- 2007
-
Abstract
- The mutational escape of HIV-1 from established CTL responses is becoming evident. However, it is not yet clear whether antigenic variations of HIV-1 may have an additional effect on the differential antiviral effectiveness of HIV-specific CTLs. Herein, we characterized HIV-specific CTL responses toward Pol, Env, and Nef optimal epitopes presented by HLA-B*35 during a chronic phase of HIV-1 infection. We found CTL escape variants within Pol and Nef epitopes that affected recognition by TCRs, although there was no mutation within the Env epitope. An analysis of peptide-HLA tetrameric complexes revealed that CD8 T cells exclusively specific for the Nef variant were generated following domination by the variant viruses. The variant-specific cells were capable of killing target cells and producing antiviral cytokines but showed impaired Ag-specific proliferation ex vivo, whereas wild-type specific cells had potent activities. Moreover, clonotypic CD8 T cells specific for the Pol variant showed diminished proliferation, whereas Env-specific ones had no functional heterogeneity. Taken together, our data indicate that antigenic variations that abolished TCR recognition not only resulted in escape from established CTL responses but also eventually generated another subset of variant-specific CTLs having decreased antiviral activity, causing an additional negative effect on antiviral immune responses during a chronic HIV infection.
- Subjects :
- Amino Acid Sequence
Cytokines metabolism
Epitopes, T-Lymphocyte immunology
Gene Products, env chemistry
Gene Products, env genetics
Gene Products, env immunology
Gene Products, nef chemistry
Gene Products, nef genetics
Gene Products, nef immunology
Gene Products, pol chemistry
Gene Products, pol genetics
Gene Products, pol immunology
HIV Antigens immunology
HLA-B35 Antigen analysis
HLA-B35 Antigen immunology
Humans
Lymphocyte Activation
Molecular Sequence Data
Mutation
Receptors, Antigen, T-Cell immunology
T-Lymphocytes, Cytotoxic chemistry
T-Lymphocytes, Cytotoxic virology
nef Gene Products, Human Immunodeficiency Virus
Antigenic Variation
Epitopes, T-Lymphocyte genetics
HIV Antigens genetics
HIV Infections immunology
HIV-1 genetics
T-Lymphocytes, Cytotoxic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 178
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17442933
- Full Text :
- https://doi.org/10.4049/jimmunol.178.9.5513