Journal article
Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype
Proceedings of the National Academy of Sciences, Vol.104(41), pp.16233-16238
10/2007
Abstract
We studied CD8 T cell responses against HIV-1, cytomegalovirus, Epstein-Barr virus, and influenza in 128 subjects and demonstrate that polyfunctional CD8 T cell responses, also including IL-2 production and Ag-specific proliferation, are predominantly driven by virus epitopes restricted by HLA-B alleles. Interestingly, these protective CD8 T cells are equipped with low-avidity T cell receptors (TCRs) for the cognate virus epitope. Conversely, HLA-Arestricted epitopes are mostly associated with "only effector" IFN-γ-secreting, with cytotoxicity, and with the lack of IL-2 production and Ag-specific proliferation. These CD8 T cells are equipped with high-avidity TCR and express higher levels of the T cell exhaustion marker PD-1. Thus, the functional profile of the CD8 T cell response is strongly influenced by the extent to which there is stimulation of polyfunctional (predominantly restricted by HLA-B) versus only effector (restricted by HLA-A) T cell responses. These results provide the rationale for the observed protective role of HLA-B in HIV-1-infection and new insights into the relationship between TCR avidity, PD-1 expression, and the functional profile of CD8 T cells.
Details
- Title
- Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype
- Authors/Creators
- A. Harari (Author/Creator)C. Cellerai (Author/Creator)F.B. Enders (Author/Creator)J. Kostler (Author/Creator)L. Codarri (Author/Creator)G. Tapia (Author/Creator)O. Boyman (Author/Creator)E. Castro (Author/Creator)S. Gaudieri (Author/Creator)I. James (Author/Creator)M. John (Author/Creator)R. Wagner (Author/Creator)S. Mallal (Author/Creator)G. Pantaleo (Author/Creator)
- Publication Details
- Proceedings of the National Academy of Sciences, Vol.104(41), pp.16233-16238
- Publisher
- National Academy of Sciences
- Identifiers
- 991005540762907891
- Copyright
- © 2007 by The National Academy of Sciences of the USA.
- Murdoch Affiliation
- Centre for Clinical Immunology and Biomedical Statistics
- Language
- English
- Resource Type
- Journal article
UN Sustainable Development Goals (SDGs)
This output has contributed to the advancement of the following goals:
Source: InCites
Metrics
205 File views/ downloads
96 Record Views
InCites Highlights
These are selected metrics from InCites Benchmarking & Analytics tool, related to this output
- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.46 HIV Pathogenesis
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology