Omicron: The role of T cells

Representation of two T cell colliding.
A new study investigates how T cells can help in the fight against Omicron. Biwa Studio/Getty Images
  • Alongside antibodies, T cells are a key player in the immune response against pathogens.
  • The Omicron variant of SARS-CoV-2 has many mutations, which means it can evade the antibody response.
  • However, the present study suggests that T cells should still offer protection against the variant.

In a new study, researchers have found evidence that T cells should offer protection against the Omicron variant of SARS-CoV-2.

The research, which appears in the journal Viruses, lays the ground for further studies to confirm the findings.

T cells

T cells play a number of roles in the immune system. Prof. Rosemary Boyton, from the Faculty of Medicine, Department of Infectious Disease at Imperial College London in the United Kingdom, explains:

“T cells can play different roles. They can act as ‘killer cells,’ attacking cells which have been infected with a virus or another kind of pathogen, or they can act as ‘helper cells’ by supporting B cells to produce antibodies.”

Prof. Florian Kern, chair of Immunology at the Brighton and Sussex Medical School, U.K., spoke with Micro B Life. He explained that T cells do this by recognizing protein fragments made up of short amino acid chains, also known as peptides. Prof. Kern was not involved in the present study.

T cells also need the peptides to be bound to specialized cell surface proteins known as MHC molecules.

“In vaccinated individuals or those with a prior history of COVID-19, memory T cells will respond quickly if they encounter the same viral peptides bound to the same MHC molecules again.”

“However, if the peptides they originally recognized are no longer present in the virus as a consequence of mutations, these memory T cells could have lost their purpose. This depends on whether the mutated peptides can still be recognized by them,” said Prof. Kern.

The Omicron variant of SARS-CoV-2 has many mutations, which scientists believe help it escape neutralizing antibodies.

However, if Omicron cannot escape T cells, then they may still have a level of protection against the variant.

Viral fragments

To identify whether Omicron can escape the T cell response, the researchers analyzed 1,500 SARS-CoV-2 epitopes — a type of viral fragment.

“The authors effectively downloaded a list of recognized SARS-CoV-2 peptides from a public repository and aligned them to the mutated protein amino acid sequence of the Omicron variant.”

“This allowed them to identify exactly which of the peptides recognized in earlier viral variants no longer existed with exactly the same sequence in the Omicron variant,” said Prof. Kern.

Summarizing the findings, Prof. Gary McLean, professor of molecular immunology at London Metropolitan University, U.K., who was not involved in the study, said to MBL that a person’s T cell immunity to the Omicron variant should still offer some protection:

“This is a bioinformatics-based study looking at T cell epitopes found in the SARS-CoV-2 Omicron variant. It identifies that the great majority of predicted Omicron spike T cell epitopes are not altered in this variant, which suggests that existing T cell immunity to Omicron from vaccination or natural infection should not be affected too badly.”

Prof. Kern agreed. “The authors subjected the relevant altered peptide sequences found in Omicron to a number of computer algorithms that are good at predicting if certain peptides can bind to certain MHC molecules. They found that only some of these peptides had probably lost the ability to bind to the same MHC molecules as their non-mutated predecessors.”

“This gave them confidence that the vast majority of peptides that are important for the T cell response to SARS-CoV-2 were not affected by the mutations found in Omicron and would still bind to the MHC molecules that the non-mutated sequences bound to.”

– Prof. Florian Kern

Prof. McLean noted that “[t]he limitation [of the study] is that there are no biological studies to support the findings. For that reason, the study results are somewhat preliminary.”

“At the same time, it is not surprising that T cell epitopes are less affected in this variant. This phenomenon is also known to occur with other human respiratory viruses, and signals that T cell immunity to SARS-CoV-2, once established, is potentially more broadly protective and [may be more] important than antibodies.”

“Although antibodies are effective at neutralizing SARS-CoV-2, mutations within the spike protein in new variants often result in reduced ability of the preexisting antibodies to do so.”

“These data may indicate that T cell immunity is more protective than antibodies against severe disease caused by Omicron, supporting some of the recent clinical findings,” Prof. McLean suggested.

Prof. Matthew McKay, co-lead author of the research from the University of Melbourne in Australia, says, “Despite being a preliminary study, we believe this is positive news.”

“Even if Omicron — or some other variant, for that matter — can potentially escape antibodies, a robust T cell response can still be expected to offer protection and help to prevent significant illness.”

T cell evasion

Speaking to MBL, Dr. Ahmed Abdul Quadeer, co-lead author of the study from the Department of Electronic and Computer Engineering at the Hong Kong University of Science and Technology, said that it may be unlikely that a variant could emerge that would evade a person’s T cell immune response.

“Evading T cell responses might be relatively difficult. This is because, in contrast to neutralizing antibodies that mainly recognize the spike (surface) protein of SARS-CoV-2, T cells recognize fragments from multiple proteins of the virus.”

“Thus, the T cells induced by [SARS-CoV-2] infection are quite heterogeneous. Even within the spike protein, which is the main target antigen of multiple COVID-19 vaccines, studies have demonstrated that several epitopes are targeted in each individual.”

“In order to evade such a broad immune response, the virus would need to make significantly more mutations than what we have seen so far, which might not be viable for the virus,” said Dr. Quadeer.

Prof. McLean agreed. “Overall, it is less likely that variants escaping T cell immunity will appear, as the T cell epitopes are often under less pressure to change, unlike the antibody epitopes, which tend to cluster in surface areas of the spike that have a critical function allowing entry of the virus into cells.”

“T cells operate by seeking out and destroying cells infected with virus, targeting different parts of the spike compared [with] antibodies, thereby tolerating mutations found in new variants.”

Natural infection or vaccination?

Dr. Quadeer said that T cells would likely offer protection whether they were developed following vaccination or a natural infection — however, further research is needed to confirm this.

“Both natural infection and COVID-19 vaccines have been demonstrated to generate a strong T cell response. However, there is a lot to understand about the specific differences and similarities between T cell responses elicited from natural infection and vaccines. This is currently being actively studied.”

“There are some obvious dissimilarities between the two responses based on the composition of COVID-19 vaccines.”

“For spike-focused vaccines, the T cell responses have been shown to recognize multiple epitopes of the spike protein. For whole-virus inactivated vaccines, while the literature is comparatively scarce, T cell responses have been shown to target, in addition to the spike protein, other structural proteins, such as the nucleocapsid and membrane proteins.”

“In the case of [SARS-CoV-2] infection, T cells have been found to target fragments from multiple proteins of the virus by numerous experimental studies conducted using blood from individuals across different geographical regions — for a review, see our previous work.”

“Similarities between the T cell responses elicited by vaccines and natural infection have also been shown by emerging studies. For example, some studies have reported that similar fragments are targeted by T cells elicited by both [SARS-CoV-2] infection and vaccines,” Dr. Quadeer explained.

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