Non-Classical MHC-1 Class 1b HLA-E Expression Levels Are Maintained in HIV-1 Infected CD4 Positive T Cells
Jason Wicker, Paul Goepfert, Steffanie Sabbaj. University of Alabama at Birmingham, Birmingham, AL
Background: HLA-E is a non-classical major histocompatibility complex (MHC) class 1b molecule that is expressed on virtually all cells. Binding of the HLA-E ligand to the natural killer (NK) cell inhibitory receptor CD94/NKG2A is sufficient to protect cells from NK cell mediated lysis. Infection of CD4 positive T lymphocytes with HIV-1 leads to significant downregulation of CD4 and classical MHC class 1a HLA-A and HLA-B expression. Although a few studies have reported increased HLA-E expression with HIV-1 infection, this effect is not well characterized. In this study, we sought to determine the effects of HIV-1 infection on HLA-E expression levels in CD4 positive T cells.
Design: Stimulated peripheral blood mononuclear cells from healthy volunteer donors were depleted of CD8 positive T cells and infected with the NL4-3 HIV-1 virus strain at varying multiplicities of infection. Cells were harvested at 2 days, 4 days, 7 days, and 10 days, and flow cytometry was utilized to determine expression levels of CD3, CD4, HIV-1 p24, HLA-A,B,C, and HLA-E. Expression of HLA-E in infected p24 positive cells was compared to levels in uninfected p24 negative cells at each timepoint.
Results: Following infection with HIV-1, significant p24 expression was identified in a subpopulation of CD3 positive T cells with low or negative expression of CD4 (mean peak infection of 9.5% of total T lymphocytes). This subpopulation of p24 positive T cells exhibited persistent downregulation of MHC-1 HLA-A and B beginning at the day 4 timepoint and continuing throughout the remainder of the experiment, relative to the p24 negative T cells (mean 72% downregulation). However, no persistent enhancement or downregulation of HLA-E expression was observed in p24 positive T cells compared to p24 negative T cells. HLA-E expression levels remained constant in HIV-1 infected CD4 positive T cells in contrast to the markedly decreased expression of HLA-A and B.
Conclusions: Review of the literature shows that various studies have come to different conclusions as to whether HLA-E expression is actively enhanced or remains stable in HIV-1 infected cells. In these experiments, our data suggest that HLA-E expression remains stable in CD4 positive T cells following infection with HIV-1 while HLA-A and B expression is markedly decreased. This selective downregulation of the classical MHC-1 class 1a molecules with maintenance of HLA-E expression allows infected cells to escape NK cell mediated lysis. Further studies seek to identify potential viral products that may be involved in the relative stabilization of HLA-E expression.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 255, Wednesday Morning