LA JOLLA – In a new article, scientists at the La Jolla Institute of Immunology (LJI) bring together research from COVID-19 researchers around the world. The results are remarkable: human T cells can target more than 1,400 sites of the SARS-CoV-2 virus.

“Our laboratory and many others have shown this very broad and diverse T-cell response,” says LJI research assistant Professor Daniela Weiskopf, Ph.D., co-author of the Cell Host & Microbe Review.

This type of review of research, known as ‘meta-analysis’, bundles the results of multiple studies and researchers take into account exactly how the studies were conducted.

In the case of COVID-19, a global meta-analysis of T-cell response studies is particularly helpful because different patient populations can have very different immune responses due to their genetic differences and past medical history.

“This really underscores that the investigation of SARS-CoV-2 was a global endeavor,” says LJI Professor Alessandro Sette, Dr. Biol.Sci, senior author of the review and a member of the LJI Center for Infectious Diseases and Vaccine Research. “Combining information from the different laboratories is a powerful thing.”

Important points:

  • The researchers evaluated all 25 known human T cell response studies conducted between the start of the COVID-19 pandemic and March 15, 2021.
  • The studies show human T cell responses against 1,434 CD4 and CD8 epitopes. Epitopes are sites on SARS-CoV-2 that T cells can recognize.
  • Grouping these studies for this larger analysis revealed several “immunodominant” sites on the virus. This is where T cells are most susceptible to homing-ons.
  • This broad T-cell response makes it difficult for SARS-CoV-2 variants to acquire enough mutations to “escape” the body’s response to the virus.

Sette adds that this analysis can help researchers monitor whether T cells show effective responses when faced with viral variants and vaccines. “Knowing which key spots are on the SARS-CoV-2 spike protein is especially important for monitoring immune responses to COVID-19 vaccines,” he says.

Despite these encouraging results, the review is limited. The researchers emphasize that current studies include mostly Caucasian participants. By expanding this research to include many ethnic groups, researchers can better understand the differences in COVID-19 mortality.

In particular, the researchers want to understand how variations in the human leukocyte antigen (HLA) system affect T cell responses. The HLA molecules of the immune system control which epitopes a T cell can “see”. The abundance of different HLA molecule types varies between ethnic groups. Therefore, research needs to consider how these differences affect T cell responses and the potential severity of the COVID-19 case.

“This is a global pandemic, so it is important that we expand our studies,” says LJI instructor Alba Grifoni, Ph.D., who served as lead author of the review.

The new review also underscores the value of the Immune Epitope Database (IEDB), a free, LJI-powered resource funded by the National Institute for Allergies and Infectious Diseases (NIAID). By adding the known epitope data to the IEDB, the researchers were able to view the various study results side by side.

“We know that there is a strong T-cell response to SARS-CoV-2,” says Grifoni. “Now we’re trying to find out where we have knowledge gaps.”

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The review “SARS-CoV-2 epitopes of human T cells: Adaptive immune response against COVID-19” was supported by the National Institute of Health (Contracts 75N93019C00001 and 75N9301900065).

Other authors of the review include John Sidney, Randi Vita, Bjoern Peters, and Shane Crotty.

DOI: 10.1016 / j.chom.2021.05.010

Via the La Jolla Institute for Immunology

The La Jolla Institute of Immunology is dedicated to understanding the intricacies and power of the immune system so that we can apply this knowledge to benefit human health and prevent a wide variety of diseases. Since it was founded in 1988 as an independent, not-for-profit research organization, the institute has made numerous advances that have led to its goal: life without disease.

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