What are T cells and how do they help immunity?

COVID-19 vaccines currently rolled out worldwide induce a potent antibody response, protecting vaccinated people against severe disease and death.

The antibodies that vaccines generate act against the spike protein SARS-CoV2 uses to invade our cells. But as variants emerge, there are concerns that antibodies’ reduced ability to stop the infection will make vaccines less effective.

The immune response is a team effort

Vaccine-induced antibodies are our first line of defence against the virus as it enters our body. They sit in our airways and float in our blood. As they encounter the virus, they immediately recognise and neutralise its spike protein blocking it from invading our cells.

To effectively prevent infection, antibodies need to match the spike protein. If this varies even slightly, antibodies might not recognise it, and the virus is free to make its way to cells and replicate.

Current COVID-19 vaccines are based on the original strain first identified in Wuhan, so they elicit antibodies that perfectly fit the spike protein of that strain. However, variants of concern have slightly changed the spike protein, so scientists worry that vaccine-induced antibodies might not stick perfectly to the mutant spikes and lose efficacy.

Fortunately, antibodies are not the only immune response vaccines can elicit. There are T cells, too.

When antibodies wane over time or are not effective against a specific variant, some cells are infected. That is when T cells come to the rescue.

These cells sit in our lymph nodes – the glands under the arms, and at the base of the neck, that are part of our immune system. During a viral infection, T cells can identify cells that have been infected and kill them. This mechanism prevents severe disease and ends the infection. But, unlike antibodies, it takes a few days before T cells kick in.

While antibodies limit infection, T cells clear the virus-infected cells. “It’s a team effort,” says Professor Stephanie Gras, a molecular biologist at La Trobe University.

The result is a mild or asymptomatic infection, unlikely to be transmitted to others. “T cell responses can be really important because they can ameliorate the symptoms of infection,” says Professor Nicole La Gruta, a T cell expert at Monash University.

How T cells work

In a natural infection, a virus enters a cell, seizes its machinery and starts replicating itself. However, the invaded cells can sneakily flag the invader’s presence by sticking many random fragments of the virus on its membrane. T cells recognise these flags and kill the cell to stop virus replication.

COVID-19 vaccines that contain inactivated virus or spike protein cannot produce a T cells response, explains La Gruta. But other vaccines, such as AstraZeneca and Pfizer, require cells to produce the spike protein. The exact flagging mechanism occurs – cells stick fragments of the spike on their membrane to alert the immune system. T cells activate, but the low dose of the vaccine is just enough to teach them what to look out for without triggering an infection.

“Vaccines educate your T cells to recognise these small part of the protein,” says Gras. “So if you do get an infection, the T cells keep the memory of having seen those type of protein once before and can be activated much faster.”

Will T cells save us from variants?

Unlike antibodies, T cells are good at recognising variations of the virus fragments, says Gras. That might explain why T cells generated in vaccinated people can recognise and are effective against variants of concern.

It might also explain why some COVID-19 vaccines can effectively prevent severe symptoms and death even in regions where variants circulate widely. In some cases, vaccine-induced antibodies have reduced ability to prevent infection with some variants. Nonetheless, the vaccines prevent severe disease and death because T cells can still recognise variant virus-infected cells and clear them.

T cell response is difficult to gauge, but current evidence is encouraging

T cell response is hard to measure, says La Gruta.

Antibodies generated in different people who have received the same vaccine are the same because they target the same antigen – the spike protein.

T cells target a whole range of antigens – the virus fragments that invaded cells flag on their membrane. The selection of these fragments is dictated by our genetics. That means that people who have received the same vaccine might flag different fragments, so their T cell response is different.

Assays to measure T cell response require large blood samples from patients and can be complex and costly to perform.

But recent studies showing a strong T cell response in patients who have recovered from COVID-19 nine months after infection are encouraging.

Another study showed that patients who recovered from SARS – the disease associated with SARS-CoV infection – had T cells able to recognise SARS-CoV 17 years after the SARS outbreak in 2003.

“There is good hope that we will be protected for a long time,” says Gras.

The T cell response some vaccines elicit might not stop us from getting infected with variants. But it might prevent us from getting severely sick, effectively turning a nasty virus into something similar to the common cold.

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