Details

Autor(en) / Beteiligte

• Romero-Martín, Luis
• Duran-Castells, Clara
• Olivella, Mireia
• Rosás-Umbert, Míriam
• Ruiz-Riol, Marta
• Sanchez, Jorge
• Hartigan-O Connor, Dennis
• Mothe, Beatriz
• Olvera, Àlex
• Brander, Christian

Titel

Disruption of the HLA-E/NKG2X axis is associated with uncontrolled HIV infections

Ist Teil von

• Frontiers in immunology, 2022-11, Vol.13, p.1027855-1027855

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• The contribution of the HLA-E/NKG2X axis in NK-mediated control of HIV infection remains unclear. We have studied the relationship between HLA-E expression and phenotypical as well as functional characteristics of NK cells, in the context of chronic HIV infection and in an model of acute infection. High viremia in HIV+ individuals was related to increased HLA-E expression, and changes in NK subpopulations, especially a reduction of the CD56 as well as an increase in adaptive NK subpopulation. Uncontrolled HIV infection was also characterized by a reversion of the NKG2A/NKG2C expression ratio and a loss of positive and negative regulation of NK mediated by HLA-E. This was reflected in a lower cytotoxic, degranulation and cytokine production capacity, especially in CD56 and adaptive NK. In line with these results, HLA-E expression showed a positive correlation with viral growth inhibition in an model of acute infection at day 7, which was lost after 14 days of culture. Using HLA-E expressing K562 cells, we determined that only one out of 11 described HIV-derived HLA-E epitopes increased HLA-E surface stability. In spite of that, eight of the 11 epitopes were capable of increasing degranulation and three drove differences in NK-cell mediated cell lysis or cytokine secretion. In conclusion, our results indicate that HLA-E molecules presenting HIV-derived epitopes may sensitize target cells for NK lysis in early HIV infection. However, prolonged exposure to elevated HLA-E expression levels may lead to NK cell dysfunction and reduced viral control In chronic infection.