PMID- 34919800
OWN - NLM
STAT- MEDLINE
DCOM- 20220110
LR  - 20220514
IS  - 2211-1247 (Electronic)
VI  - 37
IP  - 13
DP  - 2021 Dec 28
TI  - HLA-A( *)02:01 restricted T cell receptors against the highly conserved SARS-CoV-2 
      polymerase cross-react with human coronaviruses.
PG  - 110167
LID - S2211-1247(21)01667-3 [pii]
LID - 10.1016/j.celrep.2021.110167 [doi]
AB  - Cross-reactivity and direct killing of target cells remain underexplored for 
      severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific CD8(+) 
      T cells. Isolation of T cell receptors (TCRs) and overexpression in allogeneic 
      cells allows for extensive T cell reactivity profiling. We identify SARS-CoV-2 
      RNA-dependent RNA polymerase (RdRp/NSP12) as highly conserved, likely due to its 
      critical role in the virus life cycle. We perform single-cell TCRalphabeta sequencing in 
      human leukocyte antigen (HLA)-A( *)02:01-restricted, RdRp-specific T cells from 
      SARS-CoV-2-unexposed individuals. Human T cells expressing these TCRalphabeta constructs 
      kill target cell lines engineered to express full-length RdRp. Three TCR 
      constructs recognize homologous epitopes from common cold coronaviruses, 
      indicating CD8(+) T cells can recognize evolutionarily diverse coronaviruses. 
      Analysis of individual TCR clones may help define vaccine epitopes that can 
      induce long-term immunity against SARS-CoV-2 and other coronaviruses.
CI  - Copyright (c) 2021 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Nesterenko, Pavlo A
AU  - Nesterenko PA
AD  - Molecular Biology Institute, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA.
FAU - McLaughlin, Jami
AU  - McLaughlin J
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Tsai, Brandon L
AU  - Tsai BL
AD  - Department of Human Genetics, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA; Department of Urology, University of California, Los Angeles, Los 
      Angeles, CA 90095, USA; Institute for Precision Health, University of California, 
      Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, 
      University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe 
      Broad Center of Regenerative Medicine and Stem Cell Research, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Burton Sojo, Giselle
AU  - Burton Sojo G
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Cheng, Donghui
AU  - Cheng D
AD  - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, 
      University of California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Zhao, Daniel
AU  - Zhao D
AD  - Department of Human Genetics, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA; Department of Urology, University of California, Los Angeles, Los 
      Angeles, CA 90095, USA; Institute for Precision Health, University of California, 
      Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, 
      University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe 
      Broad Center of Regenerative Medicine and Stem Cell Research, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Mao, Zhiyuan
AU  - Mao Z
AD  - Department of Molecular and Medical Pharmacology, University of California, Los 
      Angeles, Los Angeles, CA 90095, USA.
FAU - Bangayan, Nathanael J
AU  - Bangayan NJ
AD  - Department of Molecular and Medical Pharmacology, University of California, Los 
      Angeles, Los Angeles, CA 90095, USA.
FAU - Obusan, Matthew B
AU  - Obusan MB
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Su, Yapeng
AU  - Su Y
AD  - Institute for Systems Biology, Seattle, WA 98109, USA.
FAU - Ng, Rachel H
AU  - Ng RH
AD  - Institute for Systems Biology, Seattle, WA 98109, USA; Department of 
      Bioengineering, University of Washington, Seattle, WA 98105, USA.
FAU - Chour, William
AU  - Chour W
AD  - Institute for Systems Biology, Seattle, WA 98109, USA; Division of Biology and 
      Biological Engineering, California Institute of Technology, Pasadena, CA 91125, 
      USA; Keck School of Medicine, University of Southern California, Los Angeles, CA 
      90033, USA.
FAU - Xie, Jingyi
AU  - Xie J
AD  - Institute for Systems Biology, Seattle, WA 98109, USA; Department of 
      Bioengineering, University of Washington, Seattle, WA 98105, USA.
FAU - Li, Yan-Ruide
AU  - Li YR
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Lee, Derek
AU  - Lee D
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Noguchi, Miyako
AU  - Noguchi M
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Carmona, Camille
AU  - Carmona C
AD  - Division of Infectious Diseases, Department of Medicine, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Phillips, John W
AU  - Phillips JW
AD  - Department of Microbiology, Immunology, and Molecular Genetics, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Kim, Jocelyn T
AU  - Kim JT
AD  - Division of Infectious Diseases, Department of Medicine, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Yang, Lili
AU  - Yang L
AD  - Molecular Biology Institute, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, 
      University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson 
      Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell 
      Research, University of California, Los Angeles, Los Angeles, CA 90095, USA.
FAU - Heath, James R
AU  - Heath JR
AD  - Institute for Systems Biology, Seattle, WA 98109, USA; Parker Institute for 
      Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 
      90095, USA.
FAU - Boutros, Paul C
AU  - Boutros PC
AD  - Department of Human Genetics, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA; Department of Urology, University of California, Los Angeles, Los 
      Angeles, CA 90095, USA; Institute for Precision Health, University of California, 
      Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, 
      University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe 
      Broad Center of Regenerative Medicine and Stem Cell Research, University of 
      California, Los Angeles, Los Angeles, CA 90095, USA; Department of Molecular and 
      Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 
      90095, USA.
FAU - Witte, Owen N
AU  - Witte ON
AD  - Molecular Biology Institute, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, 
      University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson 
      Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, 
      CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell 
      Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; 
      Department of Molecular and Medical Pharmacology, University of California, Los 
      Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, 
      University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic 
      address: owenwitte@mednet.ucla.edu.
LA  - eng
GR  - R01 CA264090/CA/NCI NIH HHS/United States
GR  - U24 CA248265/CA/NCI NIH HHS/United States
GR  - U01 CA233074/CA/NCI NIH HHS/United States
GR  - T32 CA009056/CA/NCI NIH HHS/United States
GR  - K08 AI155232/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211210
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-A*02:01 antigen)
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Immunodominant Epitopes)
RN  - 0 (RNA, Viral)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Antigen, T-Cell, alpha-beta)
RN  - 0 (Spike Glycoprotein, Coronavirus)
RN  - EC 2.7.7.48 (Coronavirus RNA-Dependent RNA Polymerase)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - COVID-19/immunology/therapy
MH  - Cell Culture Techniques
MH  - Coronavirus RNA-Dependent RNA Polymerase/*immunology
MH  - Cross Reactions/immunology
MH  - Epitopes, T-Lymphocyte/immunology
MH  - HLA-A Antigens/immunology
MH  - HLA-A2 Antigen/genetics/*immunology
MH  - Humans
MH  - Immunodominant Epitopes/immunology
MH  - Leukocytes, Mononuclear/immunology/metabolism/virology
MH  - RNA, Viral/genetics
MH  - Receptors, Antigen, T-Cell/immunology
MH  - Receptors, Antigen, T-Cell, alpha-beta/genetics/immunology
MH  - SARS-CoV-2/*immunology/pathogenicity
MH  - Spike Glycoprotein, Coronavirus/immunology
PMC - PMC8660260
OTO - NOTNLM
OT  - CD8
OT  - COVID-19
OT  - SARS-CoV-2
OT  - T cells
OT  - TCR
OT  - antigen
OT  - cell therapy
OT  - immune response
OT  - single-cell
OT  - specific
COIS- Declaration of interests O.N.W., J.M., and P.A.N. are inventors of a patent 
      application in progress that will be filed prior to manuscript publication. 
      J.R.H. is a board member of PACT Pharma and Isoplexis. O.N.W. currently has 
      consulting, equity, and/or board relationships with Trethera Corporation, Kronos 
      Biosciences, Sofie Biosciences, Breakthrough Properties, Vida Ventures, Nammi 
      Therapeutics, Two River, Iconovir, Appia BioSciences, Neogene Therapeutics, and 
      Allogene Therapeutics. None of these companies contributed to or directed any of 
      the research reported in this article.
EDAT- 2021/12/18 06:00
MHDA- 2022/01/11 06:00
PMCR- 2021/12/10
CRDT- 2021/12/17 20:09
PHST- 2021/08/11 00:00 [received]
PHST- 2021/10/15 00:00 [revised]
PHST- 2021/12/02 00:00 [accepted]
PHST- 2021/12/18 06:00 [pubmed]
PHST- 2022/01/11 06:00 [medline]
PHST- 2021/12/17 20:09 [entrez]
PHST- 2021/12/10 00:00 [pmc-release]
AID - S2211-1247(21)01667-3 [pii]
AID - 110167 [pii]
AID - 10.1016/j.celrep.2021.110167 [doi]
PST - ppublish
SO  - Cell Rep. 2021 Dec 28;37(13):110167. doi: 10.1016/j.celrep.2021.110167. Epub 2021 
      Dec 10.