Disruption of the HLA-E/NKG2X axis is associated with uncontrolled HIV infections
Romero-Martín, Luis (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Duran-Castells, Clara (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Olivella, Mireia (Universitat de Vic - Universitat Central de Catalunya)
Rosás-Umbert, Miriam (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Ruiz Riol, Marta (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Sanchez, Jorge (Impacta)
Hartigan-O'Connor, Dennis (University of California)
Mothe, Beatriz (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Olvera, Alex (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Brander, Christian (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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 in vitro 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 bright 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 bright and adaptive NK. In line with these results, HLA-E expression showed a positive correlation with viral growth inhibition in an in vitro 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 in vivo may lead to NK cell dysfunction and reduced viral control In chronic infection.
Ajuts:	Instituto de Salud Carlos III PI17/01465
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	HIV ; Natural Killer cells ; HLA-E ; NKG2A ; NKG2C
Publicat a:	Frontiers in immunology, Vol. 13 (november 2022) , ISSN 1664-3224

DOI: 10.3389/fimmu.2022.1027855
PMID: 36466823

20 p, 11.4 MB

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