PMID- 37264229
OWN - NLM
STAT- MEDLINE
DCOM- 20230630
LR  - 20231213
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 24
IP  - 7
DP  - 2023 Jul
TI  - HLA class I signal peptide polymorphism determines the level of 
      CD94/NKG2-HLA-E-mediated regulation of effector cell responses.
PG  - 1087-1097
LID - 10.1038/s41590-023-01523-z [doi]
AB  - Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C 
      and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and 
      CD94/NKG2C receptors expressed on natural killer and T cell subsets. We show that 
      among 16 common classical HLA class I SP variants, only 6 can be efficiently 
      processed to generate epitopes that enable CD94/NKG2 engagement, which we term 
      'functional SPs'. The single functional HLA-B SP, known as HLA-B/-21M, induced 
      high HLA-E expression, but conferred the lowest receptor recognition. 
      Consequently, HLA-B/-21M SP competes with other SPs for providing epitope to 
      HLA-E and reduces overall recognition of target cells by CD94/NKG2A, calling for 
      reassessment of previous disease models involving HLA-B/-21M. Genetic population 
      data indicate a positive correlation between frequencies of functional SPs in 
      humans and corresponding cytomegalovirus mimics, suggesting a means for viral 
      escape from host responses. The systematic, quantitative approach described 
      herein will facilitate development of prediction algorithms for accurately 
      measuring the impact of CD94/NKG2-HLA-E interactions in disease 
      resistance/susceptibility.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
FAU - Lin, Zhansong
AU  - Lin Z
AUID- ORCID: 0000-0001-9714-442X
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
FAU - Bashirova, Arman A
AU  - Bashirova AA
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD, USA.
AD  - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 
      Cancer Institute, Bethesda, MD, USA.
FAU - Viard, Mathias
AU  - Viard M
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD, USA.
AD  - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 
      Cancer Institute, Bethesda, MD, USA.
FAU - Garner, Lee
AU  - Garner L
AUID- ORCID: 0000-0003-3799-0266
AD  - Centre for Immuno-Oncology, University of Oxford, Oxford, UK.
FAU - Quastel, Max
AU  - Quastel M
AUID- ORCID: 0000-0001-6551-4713
AD  - Centre for Immuno-Oncology, University of Oxford, Oxford, UK.
FAU - Beiersdorfer, Maya
AU  - Beiersdorfer M
AD  - Leibniz Institute of Virology, Hamburg, Germany.
AD  - 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
AD  - German Center for Infection Research (DZIF), Site Hamburg-Lubeck-Borstel-Riems, 
      Hamburg, Germany.
FAU - Kasprzak, Wojciech K
AU  - Kasprzak WK
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD, USA.
AD  - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 
      Cancer Institute, Bethesda, MD, USA.
AD  - Advanced Biomedical Computational Science, Frederick National Laboratory for 
      Cancer Research, Frederick, MD, USA.
FAU - Akdag, Marjan
AU  - Akdag M
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD, USA.
AD  - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 
      Cancer Institute, Bethesda, MD, USA.
FAU - Yuki, Yuko
AU  - Yuki Y
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD, USA.
AD  - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 
      Cancer Institute, Bethesda, MD, USA.
FAU - Ojeda, Pedro
AU  - Ojeda P
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
FAU - Das, Sudipto
AU  - Das S
AD  - Cancer Research Technology Program, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Andresson, Thorkell
AU  - Andresson T
AD  - Cancer Research Technology Program, Frederick National Laboratory for Cancer 
      Research, Frederick, MD, USA.
FAU - Naranbhai, Vivek
AU  - Naranbhai V
AD  - Massachusetts General Hospital Cancer Center, Division of Hematology/Oncology, 
      Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
AD  - Dana-Farber Cancer Institute, Boston, MA, USA.
AD  - Center for the AIDS Programme of Research in South Africa, Durban, South Africa.
FAU - Horowitz, Amir
AU  - Horowitz A
AD  - Department of Oncological Sciences, Precision Immunology Institute, Tisch Cancer 
      Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
FAU - McMichael, Andrew J
AU  - McMichael AJ
AUID- ORCID: 0000-0002-9101-7478
AD  - Centre for Immuno-Oncology, University of Oxford, Oxford, UK.
FAU - Hoelzemer, Angelique
AU  - Hoelzemer A
AD  - Leibniz Institute of Virology, Hamburg, Germany.
AD  - 1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, 
      Germany.
AD  - German Center for Infection Research (DZIF), Site Hamburg-Lubeck-Borstel-Riems, 
      Hamburg, Germany.
FAU - Gillespie, Geraldine M
AU  - Gillespie GM
AUID- ORCID: 0000-0002-1075-870X
AD  - Centre for Immuno-Oncology, University of Oxford, Oxford, UK.
FAU - Garcia-Beltran, Wilfredo F
AU  - Garcia-Beltran WF
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
FAU - Carrington, Mary
AU  - Carrington M
AUID- ORCID: 0000-0002-2692-2180
AD  - Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. 
      carringm@mail.nih.gov.
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD, USA. carringm@mail.nih.gov.
AD  - Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National 
      Cancer Institute, Bethesda, MD, USA. carringm@mail.nih.gov.
LA  - eng
GR  - 75N91019D00024/CA/NCI NIH HHS/United States
GR  - ZIA BC010792/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20230601
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Protein Sorting Signals)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily D)
RN  - 0 (Lectins, C-Type)
RN  - 0 (Receptors, Natural Killer Cell)
SB  - IM
MH  - Humans
MH  - *Protein Sorting Signals
MH  - *Killer Cells, Natural
MH  - Histocompatibility Antigens Class I
MH  - HLA Antigens/metabolism
MH  - Histocompatibility Antigens Class II/metabolism
MH  - NK Cell Lectin-Like Receptor Subfamily D/genetics/metabolism
MH  - Lectins, C-Type/metabolism
MH  - Receptors, Natural Killer Cell/metabolism
MH  - HLA-E Antigens
PMC - PMC10690437
MID - NIHMS1943994
COIS- Competing interests The authors declare no competing interests.
EDAT- 2023/06/02 01:07
MHDA- 2023/06/30 06:42
PMCR- 2023/12/01
CRDT- 2023/06/01 23:31
PHST- 2022/08/31 00:00 [received]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/06/30 06:42 [medline]
PHST- 2023/06/02 01:07 [pubmed]
PHST- 2023/06/01 23:31 [entrez]
PHST- 2023/12/01 00:00 [pmc-release]
AID - 10.1038/s41590-023-01523-z [pii]
AID - 10.1038/s41590-023-01523-z [doi]
PST - ppublish
SO  - Nat Immunol. 2023 Jul;24(7):1087-1097. doi: 10.1038/s41590-023-01523-z. Epub 2023 
      Jun 1.