CD94 Is Essential for NK Cell-Mediated Resistance to a Lethal Viral Disease

Abstract

Summary It is well established that natural killer (NK) cells confer resistance to many viral diseases, but only in a few instances the molecular mechanisms whereby NK cells recognize virus-infected cells are known. Here we show that CD94, a molecule preferentially expressed by NK cells, is essential for the resistance of C57BL/6 mice to mousepox, a disease caused by the Orthopoxvirus ectromelia virus. Ectromelia virus-infected cells expressing the major histocompatibility complex (MHC) class Ib molecule Qa-1b are specifically recognized by the activating receptor formed by CD94 and NKG2E. Because CD94-NKG2 receptors and their ligands are highly conserved in rodents and humans, a similar mechanism may exist during human infections with the smallpox and monkeypox viruses, which are highly homologous to ectromelia virus.

Acetylcholine-producing NK cells attenuate CNS inflammation via modulation of infiltrating monocytes/macrophages

“…and the inhibitory receptor NKG2A (62)(63)(64). Results from our microassays indicated that the ChAT + NK cells had no increase of cytolytic activity, which was confirmed in vitro by a cytotoxic assay of YAC-1 cells (Fig.…”

Poxvirus Infection-Associated Downregulation of C-Type Lectin-Related-b Prevents NK Cell Inhibition by NK Receptor Protein-1B

“…In fact, NK cells with an activating Ly49 (Ly49H) are actually detrimental to the response to ECTV in C57BL/6 mice (32). Recently, it was reported that the lack of CD94 in DBA/2J mice explains their high susceptibility to ECTV (24,33). This study elegantly showed that CD94 in combination with NKG2E is essential for resistance to ECTV and synergizes with NKG2D to trigger the NK cells.…”

“…A very recent study indicates that NK cells even develop memory for VV (23). Various activating receptors on NK cells such as CD94/NKG2E and NKG2D are required for NK cell defense against ECTV in mouse (20,24), and recognition of VV infection by human NK cells involves NKG2D (25) and perhaps loss of HLA-E and classical MHC-I molecules (26,27). Moreover, certain strains of mice, particularly C57BL/6, are resistant to VV and ECTV infection (22,(28)(29)(30), and depletion of NK cells converts resistant mice to a susceptible phenotype (22).…”

Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94

“…Peptides derived from a variety of viruses, including EBV, HIV, and CMV, are known to bind to HLA-E (24-26). The HIV p24 peptide residues 14-22 (HIVp24 [14][15][16][17][18][19][20][21][22] , AISPRTLNA) was identified by a motif-based approach, and in chronic HIV infection the up-regulation of HLA-E on CD4 + T cells results in increased inhibition of NKG2A + NK cells (25,30). The peptide SQAPLPCVL from EBV BZLF-1 protein residues 39-47 (EBVbzlf [39][40][41][42][43][44][45][46][47] ) also has been shown to bind to HLA-E (24).…”

“…Expression of CD94-NKG2A is up-regulated on NK cells in HIV and HCV infection and in the latter has been associated with a poor response to treatment (11,12). Furthermore NKG2A + NK cell clones lyse vaccinia-infected targets (13), and CD94 is important in clearing mouse pox infection (14). Both KIR and CD94-NKG2A respond to MHC class I down-regulation.…”