Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype

Détails

ID Serval
serval:BIB_B0591BC8253E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Harari  A., Cellerai  C., Enders  F. B., Kostler  J., Codarri  L., Tapia  G., Boyman  O., Castro  E., Gaudieri  S., James  I., John  M., Wagner  R., Mallal  S., Pantaleo  G.
ISSN
0027-8424 (Print)
Statut éditorial
Publié
Date de publication
10/2007
Volume
104
Numéro
41
Pages
16233-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Oct 9
Résumé
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-A-restricted 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.
Pubmed
Web of science
Création de la notice
25/01/2008 16:00
Dernière modification de la notice
03/03/2018 20:34
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