Killer Ig-like receptor 2DL4 does not mediate NK cell IFN-γ responses to soluble HLA-G preparations.

The MHC class Ib molecule HLA-G has previously been reported to be the ligand for the NK cell receptor killer Ig-like receptor (KIR)2DL4, but this remains controversial. In this study, we investigated IFN-γ production by freshly isolated NK cells in response to both soluble and solid-phase ligands, including anti-KIR2DL4 mAbs and rHLA-G. Although freshly isolated CD56(bright) NK cells produced IFN-γ in response to soluble HLA-G preparations, the response was found to be absolutely dependent on the presence of small numbers of contaminating CD56(-), CD14(-), CD11c(+) myeloid dendritic cells (mDCs). HLA-G tetramers bound only to the contaminating mDCs in the NK preparations, and Abs to KIR2DL4 and HLA-G did not block NK cell IFN-γ production. NK cells did not respond to plate-bound HLA-G. Freshly isolated NK cells also produced IFN-γ in response to unpurified soluble anti-KIR2DL4 mAb but not to low endotoxin affinity-purified Ab. The data suggest that previous reports of functional interactions between KIR2DL4 and HLA-G may have resulted from the use of purified NK cells that were contaminated with mDCs and HLA-G preparations that were contaminated with material capable of stimulating mDCs to produce cytokines that stimulate NK cells to produce IFN-γ.

Monkeypox: Key questions answered.

Cases are rising worldwide, leaving some people anxious that the virus could evolve into a pandemic alongside covid-19. Michael Le Page addresses monkeypox's risks.

The risks from covid-19 reinfection.

A study has found that people who catch the coronavirus two or three times go on to have higher rates of everything from heart disease to kidney disorders, reports Michael Le Page.

Could vaccines end the pandemic?

Nasal vaccines may stem transmission, while universal ones could target proteins in every SARS-CoV-2 variant and even other coronaviruses, reports Michael Le Page.

The next big wave is coming.

Cases of covid-19 are climbing sharply again, and China in particular faces a potential disaster if it fails to contain its biggest outbreak since 2020, reports Michael Le Page.

Another flavour of omicron.

The BA.2 variant of the coronavirus is spreading fast, but it shouldn't cause another worldwide wave, says Michael Le Page.

The next covid-19 vaccines.

Global vaccine inequality, waning immunity and evolving variants mean jabs are still needed, but new ones are unlikely in 2023, says Michael Le Page.

Monkeypox unnoticed?

The virus variant responsible for a worldwide outbreak may have been circulating in people for years, reports Michael Le Page.

Understanding omicron.

Studies are beginning to shed light on why omicron behaves so differently to other coronavirus variants, reports Michael Le Page.

The changing coronavirus.

UK efforts to track the virus's evolution and the emergence of new variants have been vital, Sharon Peacock tells Michael Le Page.

New variant gains ground.

An offshoot of the delta coronavirus variant, known as AY.4.2, appears to be more transmissible, but not more dangerous, says Michael Le Page.

Should we be worried by wild animals with covid-19?

There may be a "silent epidemic" of SARS-CoV-2 in deer in the US, and other wildlife might carry it too, finds Michael Le Page.

Stopping coronavirus variants.

We failed to prevent the emergence of omicron, but there are things we can do to halt the evolution of more variants, reports Michael Le Page.

The future of medicine unlocked.

When the covid-19 pandemic finally showcased the power of mRNA therapies, it opened the door to a medical revolution, finds Michael Le Page.

The variant race is upon us.

Several countries are at a point in their vaccination drives where immunity-escaping covid-19 variants are most likely to emerge, reports Michael Le Page.

Threats from new variants.

Mutated forms of the coronavirus from the UK and South Africa are providing fresh challenges for controlling the pandemic, reports Michael Le Page.

Will vaccines work on new variants?

Some coronavirus variants seem able to partly dodge the immune system, but there is still hope for our vaccines, reports Michael Le Page.

How much worse can variants get?

The coronavirus could turn into just another cold, but it could also evolve into something much deadlier, reports Michael Le Page.

Getting to grips with long covid.

Millions of people worldwide are experiencing lasting symptoms from covid-19. Michael Le Page, Helen Thomson, Adam Vaughan and Clare Wilson report on what we do - and don't - know so far.