PMID- 23335510
OWN - NLM
STAT- MEDLINE
DCOM- 20130515
LR  - 20231213
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 288
IP  - 12
DP  - 2013 Mar 22
TI  - Polymorphism in human cytomegalovirus UL40 impacts on recognition of human 
      leukocyte antigen-E (HLA-E) by natural killer cells.
PG  - 8679-8690
LID - S0021-9258(19)33517-3 [pii]
LID - 10.1074/jbc.M112.409672 [doi]
AB  - Natural killer (NK) cell recognition of the nonclassical human leukocyte antigen 
      (HLA) molecule HLA-E is dependent on the presentation of a nonamer peptide 
      derived from the leader sequence of other HLA molecules to CD94-NKG2 receptors. 
      However, human cytomegalovirus can manipulate this central innate interaction 
      through the provision of a "mimic" of the HLA-encoded peptide derived from the 
      immunomodulatory glycoprotein UL40. Here, we analyzed UL40 sequences isolated 
      from 32 hematopoietic stem cell transplantation recipients experiencing 
      cytomegalovirus reactivation. The UL40 protein showed a "polymorphic hot spot" 
      within the region that encodes the HLA leader sequence mimic. Although all 
      sequences that were identical to those encoded within HLA-I genes permitted the 
      interaction between HLA-E and CD94-NKG2 receptors, other UL40 polymorphisms 
      reduced the affinity of the interaction between HLA-E and CD94-NKG2 receptors. 
      Furthermore, functional studies using NK cell clones expressing either the 
      inhibitory receptor CD94-NKG2A or the activating receptor CD94-NKG2C identified 
      UL40-encoded peptides that were capable of inhibiting target cell lysis via 
      interaction with CD94-NKG2A, yet had little capacity to activate NK cells through 
      CD94-NKG2C. The data suggest that UL40 polymorphisms may aid evasion of NK cell 
      immunosurveillance by modulating the affinity of the interaction with CD94-NKG2 
      receptors.
FAU - Heatley, Susan L
AU  - Heatley SL
AD  - Department of Microbiology and Immunology, University of Melbourne, Parkville, 
      Victoria 3010, Australia.
FAU - Pietra, Gabriella
AU  - Pietra G
AD  - Department of Experimental Medicine, University of Genova, Genova 16132, Italy.
FAU - Lin, Jie
AU  - Lin J
AD  - Department of Microbiology and Immunology, University of Melbourne, Parkville, 
      Victoria 3010, Australia.
FAU - Widjaja, Jacqueline M L
AU  - Widjaja JML
AD  - Department of Microbiology and Immunology, University of Melbourne, Parkville, 
      Victoria 3010, Australia.
FAU - Harpur, Christopher M
AU  - Harpur CM
AD  - Department of Microbiology and Immunology, University of Melbourne, Parkville, 
      Victoria 3010, Australia.
FAU - Lester, Sue
AU  - Lester S
AD  - Department of Rheumatology, The Queen Elizabeth Hospital, South Australia 5011, 
      Australia.
FAU - Rossjohn, Jamie
AU  - Rossjohn J
AD  - Department of Biochemistry and Molecular Biology, Monash University, Clayton, 
      Victoria 3800, Australia.
FAU - Szer, Jeff
AU  - Szer J
AD  - Department of Clinical Haematology and Bone Marrow Transplant Service, Royal 
      Melbourne Hospital, Victoria 3050, Australia.
FAU - Schwarer, Anthony
AU  - Schwarer A
AD  - Malignant Haematology and Stem Cell Transplantation Service, The Alfred Hospital, 
      Victoria 3004, Australia.
FAU - Bradstock, Kenneth
AU  - Bradstock K
AD  - Department of Haematology, Westmead Hospital, New South Wales 2145, Australia.
FAU - Bardy, Peter G
AU  - Bardy PG
AD  - Director of Cancer Services, Royal Adelaide Hospital, South Australia 5000, 
      Australia.
FAU - Mingari, Maria Cristina
AU  - Mingari MC
AD  - Department of Experimental Medicine, University of Genova, Genova 16132, Italy; 
      IRCCS AOU San Martino-IST, Genova 16132, Italy.
FAU - Moretta, Lorenzo
AU  - Moretta L
AD  - Istituto Giannina Gaslini, Genova 16147, Italy.
FAU - Sullivan, Lucy C
AU  - Sullivan LC
AD  - Department of Microbiology and Immunology, University of Melbourne, Parkville, 
      Victoria 3010, Australia.
FAU - Brooks, Andrew G
AU  - Brooks AG
AD  - Department of Microbiology and Immunology, University of Melbourne, Parkville, 
      Victoria 3010, Australia. Electronic address: agbrooks@unimelb.edu.au.
LA  - eng
SI  - GENBANK/JQ060965
SI  - GENBANK/JQ060966
SI  - GENBANK/JQ060967
SI  - GENBANK/JQ060968
SI  - GENBANK/JQ060969
SI  - GENBANK/JQ060970
SI  - GENBANK/JQ060971
SI  - GENBANK/JQ060972
SI  - GENBANK/JQ060973
SI  - GENBANK/JQ060974
SI  - GENBANK/JQ060975
SI  - GENBANK/JQ060976
SI  - GENBANK/JQ060977
SI  - GENBANK/JQ060978
SI  - GENBANK/JQ060979
SI  - GENBANK/JQ060980
SI  - GENBANK/JQ060981
SI  - GENBANK/JQ060982
SI  - GENBANK/JQ060983
SI  - GENBANK/JQ060984
SI  - GENBANK/JQ060985
SI  - GENBANK/JQ060986
SI  - GENBANK/JQ060987
SI  - GENBANK/JQ060988
SI  - GENBANK/JQ060989
SI  - GENBANK/JQ060990
SI  - GENBANK/JQ060991
SI  - GENBANK/JQ060992
SI  - GENBANK/JQ060993
SI  - GENBANK/JQ060994
SI  - GENBANK/JQ060995
SI  - GENBANK/JQ060996
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130118
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (KLRD1 protein, human)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily C)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily D)
RN  - 0 (UL40 glycoprotein, Cytomegalovirus)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Cells, Cultured
MH  - Cytomegalovirus/*genetics/immunology
MH  - Cytotoxicity, Immunologic
MH  - Female
MH  - Hematopoietic Stem Cell Transplantation
MH  - Histocompatibility Antigens Class I/chemistry/*metabolism/physiology
MH  - Humans
MH  - Killer Cells, Natural/*immunology/metabolism
MH  - Leukemia, Myeloid, Acute/therapy
MH  - Lymphoma, Non-Hodgkin/therapy
MH  - Male
MH  - Middle Aged
MH  - Molecular Sequence Data
MH  - NK Cell Lectin-Like Receptor Subfamily C/metabolism
MH  - NK Cell Lectin-Like Receptor Subfamily D/metabolism
MH  - Phylogeny
MH  - *Polymorphism, Genetic
MH  - Protein Binding
MH  - Sequence Analysis, DNA
MH  - Viral Proteins/chemistry/*genetics/immunology
MH  - Young Adult
MH  - HLA-E Antigens
PMC - PMC3605686
EDAT- 2013/01/22 06:00
MHDA- 2013/05/17 06:00
PMCR- 2014/03/22
CRDT- 2013/01/22 06:00
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/05/17 06:00 [medline]
PHST- 2014/03/22 00:00 [pmc-release]
AID - S0021-9258(19)33517-3 [pii]
AID - M112.409672 [pii]
AID - 10.1074/jbc.M112.409672 [doi]
PST - ppublish
SO  - J Biol Chem. 2013 Mar 22;288(12):8679-8690. doi: 10.1074/jbc.M112.409672. Epub 
      2013 Jan 18.