The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8+ T Cells in Response to a Lethal Poxvirus Infection

• Control of lethal poxvirus infection requires NKG2A
• NKG2A limits excessive activation and apoptosis within virus-specific CD8+ T cells
• NKG2C and NKG2E are not expressed on the surface of mouse NK cells and CD8+ T cells
• Qa-1 is preferentially expressed on B cells in ECTV-infected tissues

SummaryCD8+ T cells and NK cells protect from viral infections by killing virally infected cells and secreting interferon-γ. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses. NKG2A, which is encoded by Klrc1, is a lectin-like inhibitory receptor that is expressed as a heterodimer with CD94 on NK cells and activated CD8+ T cells. Previous studies on the impact of CD94/NKG2A heterodimers on anti-viral responses have yielded contrasting results and the in vivo function of NKG2A remains unclear. Here, we generated Klrc1–/– mice and found that NKG2A is selectively required for resistance to ectromelia virus (ECTV). NKG2A functions intrinsically within ECTV-specific CD8+ T cells to limit excessive activation, prevent apoptosis, and preserve the specific CD8+ T cell response. Thus, although inhibitory receptors often cause T cell exhaustion and viral spreading during chronic viral infections, NKG2A optimizes CD8+ T cell responses during an acute poxvirus infection.

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