Escape from highly effective public CD8+ T-cell clonotypes by HIV
- 25 August 2011
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 118 (8), 2138-2149
- https://doi.org/10.1182/blood-2011-01-328781
Abstract
Mapping the precise determinants of T-cell efficacy against viruses in humans is a public health priority with crucial implications for vaccine design. To inform this effort, we performed a comprehensive analysis of the effective CD8+ T-cell clonotypes that constitute responses specific for the HIV p24 Gag-derived KK10 epitope (KRWIILGLNK; residues 263-272) restricted by HLA-B*2705, which are known to confer superior control of viral replication in HIV-infected individuals. Particular KK10-specific CD8+ T-cell clonotypes, characterized by TRBV4-3/TRBJ1-3 gene rearrangements, were found to be preferentially selected in vivo and shared between individuals. These “public” clonotypes exhibit high levels of TCR avidity and Ag sensitivity, which impart functional advantages and enable effective suppression of HIV replication. The early L268M mutation at position 6 of the KK10 epitope enables the virus to avoid recognition by these highly effective CD8+ T-cell clonotypes. However, alternative clonotypes with variant reactivity provide flexibility within the overall KK10-specific response. These findings provide refined mechanistic insights into the workings of an effective CD8+ T-cell response against HIV.Keywords
This publication has 53 references indexed in Scilit:
- Convergent recombination shapes the clonotypic landscape of the naïve T-cell repertoireProceedings of the National Academy of Sciences of the United States of America, 2010
- Overlap and Effective Size of the Human CD8 + T Cell Receptor RepertoireScience Translational Medicine, 2010
- The antiviral factor APOBEC3G improves CTL recognition of cultured HIV-infected T cellsThe Journal of Experimental Medicine, 2009
- Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infectionThe Journal of Experimental Medicine, 2009
- Tricks with tetramers: how to get the most from multimeric peptide–MHCImmunology, 2009
- Rapid Culling of the CD4+ T Cell Repertoire in the Transition from Effector to MemoryImmunity, 2008
- A viral CTL escape mutation leading to immunoglobulin-like transcript 4–mediated functional inhibition of myelomonocytic cellsThe Journal of Experimental Medicine, 2007
- Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnoverThe Journal of Experimental Medicine, 2007
- HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotypeProceedings of the National Academy of Sciences of the United States of America, 2007
- Sharing of T cell receptors in antigen-specific responses is driven by convergent recombinationProceedings of the National Academy of Sciences of the United States of America, 2006