Cytotoxic T-cell recognition of HIV-1 cross-clade and clade-specific epitopes in HIV-1-infected Thai and Japanese patients

AIDS ◽  
2002 ◽  
Vol 16 (5) ◽  
pp. 701-711 ◽  
Author(s):  
Katsuhiko Fukada ◽  
Hiroko Tomiyama ◽  
Chantapong Wasi ◽  
Tomoko Matsuda ◽  
Shigeru Kusagawa ◽  
...  
2019 ◽  
Vol 93 (20) ◽  
Author(s):  
Thomas van Stigt Thans ◽  
Janet I. Akko ◽  
Annika Niehrs ◽  
Wilfredo F. Garcia-Beltran ◽  
Laura Richert ◽  
...  

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) has evolved elaborate ways to evade immune cell recognition, including downregulation of classical HLA class I (HLA-I) from the surfaces of infected cells. Recent evidence identified HLA-E, a nonclassical HLA-I, as an important part of the antiviral immune response to HIV-1. Changes in HLA-E surface levels and peptide presentation can prompt both CD8+T-cell and natural killer (NK) cell responses to viral infections. Previous studies reported unchanged or increased HLA-E levels on HIV-1-infected cells. Here, we examined HLA-E surface levels following infection of CD4+T cells with primary HIV-1 strains and observed that a subset downregulated HLA-E. Two primary strains of HIV-1 that induced the strongest reduction in surface HLA-E expression were chosen for further testing. Expression of single Nef or Vpu proteins in a T-cell line, as well as tail swap experiments exchanging the cytoplasmic tail of HLA-A2 with that of HLA-E, demonstrated that Nef modulated HLA-E surface levels and targeted the cytoplasmic tail of HLA-E. Furthermore, infection of primary CD4+T cells with HIV-1 mutants showed that a lack of functional Nef (and Vpu to some extent) impaired HLA-E downmodulation. Taken together, the results of this study demonstrate for the first time that HIV-1 can downregulate HLA-E surface levels on infected primary CD4+T cells, potentially rendering them less vulnerable to CD8+T-cell recognition but at increased risk of NKG2A+NK cell killing.IMPORTANCEFor almost two decades, it was thought that HIV-1 selectively downregulated the highly expressed HLA-I molecules HLA-A and HLA-B from the cell surface in order to evade cytotoxic-T-cell recognition, while leaving HLA-C and HLA-E molecules unaltered. It was stipulated that HIV-1 infection thereby maintained inhibition of NK cells via inhibitory receptors that bind HLA-C and HLA-E. This concept was recently revised when a study showed that primary HIV-1 strains reduce HLA-C surface levels, whereas the cell line-adapted HIV-1 strain NL4-3 lacks this ability. Here, we demonstrate that infection with distinct primary HIV-1 strains results in significant downregulation of surface HLA-E levels. Given the increasing evidence for HLA-E as an important modulator of CD8+T-cell and NKG2A+NK cell functions, this finding has substantial implications for future immunomodulatory approaches aimed at harnessing cytotoxic cellular immunity against HIV.


Cell Reports ◽  
2019 ◽  
Vol 27 (1) ◽  
pp. 142-153.e4 ◽  
Author(s):  
Blandine Monel ◽  
Annmarie McKeon ◽  
Pedro Lamothe-Molina ◽  
Priya Jani ◽  
Julie Boucau ◽  
...  

AIDS ◽  
1997 ◽  
Vol 11 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Maria H. Fernandez ◽  
Sarah J. Fidler ◽  
Richard J. Pitman ◽  
Jonathan N. Weber ◽  
Ann D.M. Rees

Author(s):  
LINDA R. GOODING ◽  
KATHRYN A. O'CONNELL ◽  
ROY GEIB ◽  
JAMES M. PIPAS

1981 ◽  
Vol 11 (9) ◽  
pp. 694-699 ◽  
Author(s):  
Lesley E. Wallace ◽  
Denis J. Moss ◽  
Alan B. Rickinson ◽  
Andrew J. McMichael ◽  
M. Anthony Epstein

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