27 research outputs found

    Presentation of an Immunodominant Immediate-Early CD8+ T Cell Epitope Resists Human Cytomegalovirus Immunoevasion.

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    Control of human cytomegalovirus (HCMV) depends on CD8+ T cell responses that are shaped by an individual's repertoire of MHC molecules. MHC class I presentation is modulated by a set of HCMV-encoded proteins. Here we show that HCMV immunoevasins differentially impair T cell recognition of epitopes from the same viral antigen, immediate-early 1 (IE-1), that are presented by different MHC class I allotypes. In the presence of immunoevasins, HLA-A- and HLA-B-restricted T cell clones were ineffective, but HLA-C*0702-restricted T cell clones recognized and killed infected cells. Resistance of HLA-C*0702 to viral immunoevasins US2 and US11 was mediated by the alpha3 domain and C-terminal region of the HLA heavy chain. In healthy donors, HLA-C*0702-restricted T cells dominated the T cell response to IE-1. The same HLA-C allotype specifically protected infected cells from attack by NK cells that expressed a corresponding HLA-C-specific KIR. Thus, allotype-specific viral immunoevasion allows HCMV to escape control by NK cells and HLA-A- and HLA-B-restricted T cells, while the virus becomes selectively vulnerable to an immunodominant population of HLA-C-restricted T cells. Our work identifies a T cell population that may be of particular efficiency in HCMV-specific immunotherapy

    Competitive experiments between human r-RV and bovine wt-RV at an MOI ratio of 1∶100.

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    <p>Competitive experiments were performed by co-infecting MA-104 cells by 0.003 PFU/cell of r-RV M1 or M3 and 0.3 PFU/cell of bovine wt-RV RF (1∶100 MOI ratio). RNA profiles of viral progenies resulting from mixed infections by wt-bovine RF virus and human r-RV M1 (A) or M3 (B). Pn indicate the passage number; numbers indicate the location of RNA segments; arrows indicate rearranged segments 7R and 7RΔ. (C) Western-blot detection of the NSP3 protein expressed by the viral progenies resulting from the M3+RF co-infection (1∶100 MOI ratio) at passage 3 (P3) and 9 (P9). Arrows indicate the NSP3 and the modified mNSP3 proteins expressed by wt-RV RF and r-RV M3, respectively. Numbers indicate molecular size, in kilodaltons.</p

    Competitive experiments between bovine wt-RV and human r-RV.

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    <p>Competitive experiments were performed by co-infecting MA-104 cells by the bovine wt-RV RF and one of the human r-RV at an MOI ratio of 1∶1 (0.3 PFU/cell for each virus). The resulting cell culture lysates were serially propagated in MA-104 cells. RNA profiles of viral progenies resulting from mixed infections by wt-bovine RF virus and human r-RV M1 (A), M3 (B), M4 (C), or M2 (D). RNA profiles of wt-bovine RF and human r-RV show differences of mobility for 8 RNA segments (segments 1, 4–6, 8–11). I and Pn indicate the initial inoculum used for mixed infections and the passage number, respectively. Numbers indicate the location of RNA segments. Arrows indicate rearranged segments 7R, 7RΔ, and 11R.</p

    Competitive experiments between human wt-RV M0 and r-RV M1 or M3.

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    <p>Competitive experiments were performed by co-infecting MA-104 cells by wt-RV and r-RV at an MOI ratio of 1∶1 (0.3 PFU/cell for each virus). The resulting cell culture lysates were serially propagated in MA-104 cells. RNA profiles of viral progenies resulting from mixed infections by wt-RV M0 and r-RV M1 (A) or M3 (B) are shown. I and Pn indicate the initial inoculum used for mixed infections and the passage number, respectively. Numbers indicate the location of RNA segments. Arrows indicate the rearranged segment 7R from M1 and 7RΔ from M3. (C) Western-blot detection of the NSP3 protein expressed by the viral progenies resulting from the M0+M3 co-infection at passage 1(P1) and 3 (P3). Arrows indicate the NSP3 and the modified mNSP3 proteins encoded by wt segment 7 (M0 virus) and rearranged segment 7RΔ (M3 virus), respectively. Numbers indicate molecular size, in kilodaltons.</p
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