Harari, Alexandre and Cellerai, Cristina and Enders, Felicitas Bellutti and Koestier, Josef and Codarri, Laura and Tapia, Gonzalo and Boyman, Onur and Castro, Erika and Gaudieri, Silvana and James, Ian and John, Mina and Wagner, Ralf and Mallal, Simon and Pantaleo, Giuseppe (2007) Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 104 (41). pp. 16233-16238. ISSN 0027-8424,
Full text not available from this repository. (Request a copy)Abstract
We studied CD8 T cell responses against HIV-1, cytornegalovirus, 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-gamma-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIV-1-INFECTED SUBJECTS; FUNCTIONAL SIGNATURES; DOMINANT INFLUENCE; AVIDITY; HIV; INFECTION; IMMUNITY; RESPONSES; EPITOPES; ALLELES; HLA genotype; PD-1 expression; functional profile; T cell avidity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Dec 2020 08:11 |
| Last Modified: | 02 Dec 2020 08:11 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32079 |
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