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Memory T cells remember coronavirus infections

Viral infections can induce memory T cells in humans. A previous infection can influence the course of a new viral infection.

As a response to pathogens, naive T cells rapidly divide and express molecules such as cytokines that fight infections. The responding cells are called effector T cells. Effector T cells can migrate into inflamed tissues and kill infected cells. After eliminating a pathogen, most of these cells die; however, a small pool of the long-lived memory cells remains ready to respond rapidly if a new infection of the same pathogen occurs.

Akondy et al. and Youngblood et al. recently studied the cell population giving rise to memory T cells and the evolution of memory T cells. DNA-methylation profiling allowed the researchers to observe how naïve T cells differentiate into effector cells. During T cell differentiation, their DNA-methylation profile changes. Methyl groups are added to many genes associated with the naïve state. Methyl groups are lost at genes encoding key components of the effector response. DNA methyltransferase Dnmt3a is the key enzyme responsible for de-novo DNA methylation during the immune response. DNA-methylation events are epigenetic modifications.

Memory T cells that no longer express effector molecules remain in a state of low methylation. Memory T cells can be present as long as ten or even 17 years after vaccination. However, when a new infection occurs, memory T cells can respond rapidly to re-express effector molecules to fight the new infection.

The two research groups found that patients who recovered from a coronavirus infection possessed long-lasting memory T cells reactive to the N protein of SARS-CoV. These T cells also showed cross-reactivity to SASRS-CoV-2. As a result, infections with betacoronaviruses induce a strong and long-lasting T cell immunity to the structural protein N. This immunity appears to last as long as 17 years or even longer.

A recent paper reported that beta-coronavirus infections in humans induce a long-lasting T cell immunity to the viral structural protein N of coronaviruses. Bert et al. studied T cell responses to structural and non-structural regions of SARS-CoV-2 (COVID-19) from patients recovering from the COVID-19.

How was the study done?

Blood samples were collected from donors recovering from a SARS-CoV-1 or SARS-CoV-2 infection. Density-gradient centrifugation enabled the isolation of peripheral blood mononuclear cells (PBMC). PBMCs are a mixture of specialized cells of the immune system. Peptide pools of 15mer peptides spanning the entire protein sequence of selected proteins allowed the stimulation of PBMCs. The analysis of stimulated cells utilized peptide array plates. Also, flow cytometry was used for the study of PBMCs or expanded T cell lines.

SARS‐CoV‐2‐specific T cell peptides

T cells in convalescent COVID‐19 patients target multiple regions of nucleocapsid protein.

 .

Type of response

Amino acid residue

 

SARS‐CoV‐2 Amino acid sequence

SARS‐CoV‐1 Amino acid sequence

CD4, C-1

NP 81‐95

DDQIGYYRRATRRIR

DDQIGYYRRATRRVR

CD8, C-1

NP 321‐340

GMEVTPSGTWLTYTGAIKLD

GMEVTPSGTWLTYHGAIKLD

CD4, C-4

NP 266‐280

KAYNVTQAFGRRGPE

KQYNVTQAFGRRGPE

CD4, C-4

NP 291‐305

LIRQGTDYKHWPQIA

LIRQGTDYKHWPQIA

CD4, C-4

NP 301‐315

WPQIAQFAPSASAFF

WPQIAQFAPSASAFF

CD4, C-8

NP 51‐65

SWFTALTQHGKEDLK

SWFTALTQHGKEELR

CD4, C-8

NP 101‐120

MKDLSPRWYFYYLGTGPEAG

MKELSPRWYFYYLGTGPEAS

C‐10, CD8, CD4

NP 321‐340

GMEVTPSGTWLTYTGAIKLD

GMEVTPSGTWLTYHGAIKLD

C‐12, CD8

NP 321‐340

GMEVTPSGTWLTYTGAIKLD

GMEVTPSGTWLTYHGAIKLD

C‐15, CD4

NP 101‐120

MKDLSPRWYFYYLGTGPEAG

MKELSPRWYFYYLGTGPEAS

C‐16, CD4

NSP7 21‐35

RVESSSKLWAQCVQL

RVESSSKLWAQCVQL

  
Reference

Nina Le Bert, Anthony T Tan, Kamini Kunasegaran, Christine Y L Tham, Morteza Hafezi, Adeline Chia, Melissa Chng, Meiyin Lin, Nicole Tan, Martin Linster, Wan Ni Chia, Mark I-Cheng Chen, Lin-Fa Wang, Eng Eong Ooi, Shirin Kalimuddin, Paul Anantharajal Tambyah, Jenny Guek-Hong Low, Yee-Joo Tan, Antonio Bertoletti; Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals. bioRxiv 2020.05.26.115832.

Memory T cell wiki

Origins of memory T cells

 

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