PMID- 33893172
OWN - NLM
STAT- MEDLINE
DCOM- 20220228
LR  - 20231213
IS  - 2470-9468 (Electronic)
IS  - 2470-9468 (Linking)
VI  - 6
IP  - 58
DP  - 2021 Apr 23
TI  - Natural killer cell receptors regulate responses of HLA-E-restricted T cells.
LID - eabe9057 [pii]
LID - 10.1126/sciimmunol.abe9057 [doi]
AB  - Human cytomegalovirus (CMV) infection can stimulate robust human leukocyte 
      antigen (HLA)-E-restricted CD8(+) T cell responses. These T cells recognize a 
      peptide from UL40, which differs by as little as a single methyl group from 
      self-peptides that also bind HLA-E, challenging their capacity to avoid 
      self-reactivity. Unexpectedly, we showed that the UL40/HLA-E T cell receptor 
      (TCR) repertoire included TCRs that had high affinities for HLA-E/self-peptide. 
      However, paradoxically, lower cytokine responses were observed from UL40/HLA-E T 
      cells bearing TCRs with high affinity for HLA-E. RNA sequencing and flow 
      cytometric analysis revealed that these T cells were marked by the expression of 
      inhibitory natural killer cell receptors (NKRs) KIR2DL1 and KIR2DL2/L3. On the 
      other hand, UL40/HLA-E T cells bearing lower-affinity TCRs expressed the 
      activating receptor NKG2C. Activation of T cells bearing higher-affinity TCRs was 
      regulated by the interaction between KIR2D receptors and HLA-C. These findings 
      identify a role for NKR signaling in regulating self/non-self discrimination by 
      HLA-E-restricted T cells, allowing for antiviral responses while avoiding 
      contemporaneous self-reactivity.
CI  - Copyright (c) 2021 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works.
FAU - Sullivan, Lucy C
AU  - Sullivan LC
AUID- ORCID: 0000-0003-2907-4989
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia. lcsull@unimelb.edu.au 
      agbrooks@unimelb.edu.au.
AD  - Lung Transplant Service, The Alfred Hospital and Monash University Melbourne, 
      Victoria 3000, Australia.
FAU - Nguyen, Thi H O
AU  - Nguyen THO
AUID- ORCID: 0000-0002-9294-7693
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Harpur, Christopher M
AU  - Harpur CM
AUID- ORCID: 0000-0002-3238-9861
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Stankovic, Sanda
AU  - Stankovic S
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Kanagarajah, Abbie R
AU  - Kanagarajah AR
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Koutsakos, Marios
AU  - Koutsakos M
AUID- ORCID: 0000-0001-9994-9723
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Saunders, Philippa M
AU  - Saunders PM
AUID- ORCID: 0000-0002-0813-7752
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Cai, Zhangying
AU  - Cai Z
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Gray, James A
AU  - Gray JA
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Widjaja, Jacqueline M L
AU  - Widjaja JML
AUID- ORCID: 0000-0002-4946-5584
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Lin, Jie
AU  - Lin J
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Pietra, Gabriella
AU  - Pietra G
AUID- ORCID: 0000-0002-7080-531X
AD  - Department of Experimental Medicine (DiMES). University of Genoa, Genoa 16132, 
      Italy.
AD  - Unita Operativa Complessa Immunologia, Ospedale Policlinico San Martino, Genoa 
      16132, Italy.
FAU - Mingari, Maria Cristina
AU  - Mingari MC
AD  - Department of Experimental Medicine (DiMES). University of Genoa, Genoa 16132, 
      Italy.
AD  - Unita Operativa Complessa Immunologia, Ospedale Policlinico San Martino, Genoa 
      16132, Italy.
AD  - Center of Excellence for Biomedical Research, University of Genoa, Genoa 16132, 
      Italy.
FAU - Moretta, Lorenzo
AU  - Moretta L
AD  - Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino 
      Gesu, 00165 Roma, Italy.
FAU - Samir, Jerome
AU  - Samir J
AUID- ORCID: 0000-0001-6557-9373
AD  - School of Medical Sciences and The Kirby Institute, UNSW, Sydney, New South 
      Wales, Australia.
FAU - Luciani, Fabio
AU  - Luciani F
AD  - School of Medical Sciences and The Kirby Institute, UNSW, Sydney, New South 
      Wales, Australia.
FAU - Westall, Glen P
AU  - Westall GP
AD  - Lung Transplant Service, The Alfred Hospital and Monash University Melbourne, 
      Victoria 3000, Australia.
FAU - Malmberg, Karl J
AU  - Malmberg KJ
AUID- ORCID: 0000-0002-8718-9373
AD  - KG Jebsen Center for Cancer Immunotherapy, Institute of Clinical Medicine, 
      University of Oslo, Oslo 0318, Norway.
AD  - Department of Cancer Immunology, Institute for Cancer Research, Oslo University 
      Hospital, Oslo 0310, Norway.
AD  - Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska 
      Institutet, 14186 Stockholm, Sweden.
FAU - Kedzierska, Katherine
AU  - Kedzierska K
AUID- ORCID: 0000-0001-6141-335X
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia.
FAU - Brooks, Andrew G
AU  - Brooks AG
AUID- ORCID: 0000-0002-4085-9683
AD  - Department of Microbiology and Immunology, University of Melbourne at the Peter 
      Doherty Institute, Parkville, Victoria 3010, Australia. lcsull@unimelb.edu.au 
      agbrooks@unimelb.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sci Immunol
JT  - Science immunology
JID - 101688624
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Receptors, Natural Killer Cell)
RN  - 0 (UL40 glycoprotein, Cytomegalovirus)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology/metabolism
MH  - Cytomegalovirus/immunology
MH  - Cytomegalovirus Infections/blood/*immunology/virology
MH  - Histocompatibility Antigens Class I/*metabolism
MH  - Humans
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - Receptors, Antigen, T-Cell/metabolism
MH  - Receptors, Natural Killer Cell/*metabolism
MH  - Viral Proteins/immunology/metabolism
MH  - HLA-E Antigens
EDAT- 2021/04/25 06:00
MHDA- 2022/03/01 06:00
CRDT- 2021/04/24 05:40
PHST- 2020/09/23 00:00 [received]
PHST- 2021/03/25 00:00 [accepted]
PHST- 2021/04/24 05:40 [entrez]
PHST- 2021/04/25 06:00 [pubmed]
PHST- 2022/03/01 06:00 [medline]
AID - 6/58/eabe9057 [pii]
AID - 10.1126/sciimmunol.abe9057 [doi]
PST - ppublish
SO  - Sci Immunol. 2021 Apr 23;6(58):eabe9057. doi: 10.1126/sciimmunol.abe9057.