Exposure to common cold coronaviruses can teach the immune system to
recognize SARS-CoV-2
Researchers caution: It is too soon to say whether pre-existing immune
cell memory affects COVID-19 clinical outcomes

Date:
August 4, 2020
Source:
La Jolla Institute for Immunology
Summary:
A new study shows that memory helper T cells that recognize common
cold coronaviruses also recognize matching sites on SARS-CoV-2,
the virus that causes COVID-19.



FULL STORY ==========================================================================
Your immune system's "memory" T cells keep track of the viruses they
have seen before. This immune cell memory gives the cells a headstart
in recognizing and fighting off repeat invaders.


==========================================================================
Now, a new study led by scientists at La Jolla Institute for Immunology
(LJI) shows that memory helper T cells that recognize common cold
coronaviruses also recognize matching sites on SARS-CoV-2, the virus
that causes COVID-19.

The research, published Aug. 4, 2020 in Science, may explain why some
people have milder COVID-19 cases than others -- though the researchers emphasize that this is speculation and much more data is needed.

"We have now proven that, in some people, pre-existing T cell memory
against common cold coronaviruses can cross-recognize SARS-CoV-2, down to
the exact molecular structures," says LJI Research Assistant Professor
Daniela Weiskopf, Ph.D., who co-led the new study with LJI Professor
Alessandro Sette, Dr. Biol.

Sci. "This could help explain why some people show milder symptoms of
disease while others get severely sick." "Immune reactivity may translate
to different degrees of protection," adds Sette. "Having a strong T
cell response, or a better T cell response may give you the opportunity
to mount a much quicker and stronger response." The new work builds
on a recent Cell paper from the Sette Lab and the lab of LJI Professor
Shane Crotty, Ph.D., which showed that 40 to 60 percent of people never
exposed to SARS-CoV-2 had T cells that reacted to the virus. Their immune systems recognized fragments of the virus it had never seen before. This finding turned out to be a global phenomenon and was reported in people
from the Netherlands, Germany, the United Kingdom and Singapore.



========================================================================== Scientists wondered if these T cells came from people who had previously
been exposed to common cold coronaviruses -- what Sette calls SARS-CoV-2's "less dangerous cousins." If so, was exposure to these cold viruses
leading to immune memory against SARS-CoV-2? For the new study, the researchers relied on a set of samples collected from study participants
who had never been exposed to SARS-CoV-2. They defined the exact
sites of the virus that are responsible for the cross-reactive T cell
response. Their analysis showed that unexposed individuals can produce
a range of memory T cells that are equally reactive against SARS-CoV-2
and four types of common cold coronaviruses.

This discovery suggests that fighting off a common cold coronavirus can
indeed teach the T cell compartment to recognize some parts of SARS-CoV-2
and provides evidence for the hypothesis that common cold viruses can,
in fact, induce cross-reactive T cell memory against SARS-CoV-2.

"We knew there was pre-existing reactivity, and this study provides very
strong direct molecular evidence that memory T cells can 'see' sequences
that are very similar between common cold coronaviruses and SARS-CoV-2,"
says Sette.

Looking closer, the researchers found that while some cross-reactive
T cells targeted the SARS-CoV-2's spike protein, the region of the
virus that recognizes and binds to human cells, pre-existing immune
memory was also directed to other SARS-CoV-2 proteins. This finding is relevant, Sette explains, since most vaccine candidates target mostly
the spike protein. These findings suggest the hypothesis that inclusion
of additional SARS-CoV-2 targets might enhance the potential to take
advantage of this cross reactivity and could further enhance vaccine
potency.

The study, "Selective and cross-reactive SARS-CoV-2 T cell epitopes
in unexposed humans," was supported by the National Institutes of
Health's National Institute for Allergy and Infectious Disease (AI42742, AI135078, UCSD T32s AI007036 and AI007384), National Institutes of Health contracts Nr.

75N9301900065 and U19 AI118626, and the John and Mary Tu Foundation.

Additional study authors include Alba Grifoni, Alison Tarke, John Sidney, Sydney I. Ramirez, Jennifer M. Dan, Zoe C. Burger, Stephen A. Rawlings,
Davey M. Smith, Elizabeth Phillips, Simon Mallal, Marshall Lammers, Paul Rubiro, Lorenzo Quiambao, Aaron Sutherland, Esther Dawen Yu, Ricardo
da Silva Antunes, Jason Greenbaum, April Frazier, Alena J. Markmann, Lakshmanane Premkumar, Aravinda de Silva, Bjoern Peters and Shane Crotty.


========================================================================== Story Source: Materials provided by
La_Jolla_Institute_for_Immunology. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Jose Mateus, Alba Grifoni, Alison Tarke, John Sidney, Sydney
I. Ramirez,
Jennifer M. Dan, Zoe C. Burger, Stephen A. Rawlings, Davey M. Smith,
Elizabeth Phillips, Simon Mallal, Marshall Lammers, Paul Rubiro,
Lorenzo Quiambao, Aaron Sutherland, Esther Dawen Yu, Ricardo da
Silva Antunes, Jason Greenbaum, April Frazier, Alena J. Markmann,
Lakshmanane Premkumar, Aravinda de Silva, Bjoern Peters,
Shane Crotty, Alessandro Sette, Daniela Weiskopf. Selective
and cross-reactive SARS-CoV-2 T cell epitopes in unexposed
humans. Science, Aug. 4, 2020; DOI: 10.1126/science.abd3871 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200804100219.htm

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